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BACKGROUND: Non-invasive Brain-Computer Interface (BCI) uses an electroencephalogram (EEG) to obtain information on brain neural activity. Because EEG can be contaminated by various artifacts during the collection process, it has primarily evolved into motor imagery (MI) with a low risk of contamination. However, MI has a disadvantage in that accurate data is difficult to obtain. OBJECTIVE: The goal of this study was to determine which motor imagery and movement execution (ME) of the knee has the best classification performance. METHODS: Ten subjects were selected to provide MI and ME data for four different types of knee exercise. The experiment was conducted to keep the left, right, and both knees extend or bend for five seconds, and there was a five seconds break between each movement. Each motion was performed 20 times and the MI was carried out in the same protocol. Motions were classified through a modified model of the Lenet-5 of CNN (Convolution Neural Network). RESULTS: The deep learning data was classified, and a study discovered that ME (98.91%) could be classified significantly more accurately than MI (98.37%) (p< 0.001). CONCLUSION: If future studies on other body movements are conducted, we anticipate that BCI can be further developed to be more accurate. And such advancements in BCI can be used to facilitate the patient’s communication by analyzing the user’s movement intention. These results can also be used for various controls such as robots using a combination of MI and ME.

The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting these events through paracrine communication. Here, we demonstrate that conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and CAFs. Direct exposure of CAFs to apoptotic 344SQ cells (ApoSQ) inhibited CAF migration and invasion and the expression of CAF activation markers. Enhanced secretion of Wnt‐induced signaling protein 1 (WISP-1) by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive effects. Pharmacological inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP-1 production by CAFs and reversed the antimigratory and anti-invasive effects. Enhanced expression of the Notch ligand delta-like protein 1 on the surface of ultraviolet-irradiated apoptotic lung cancer cells triggered Notch1-WISP-1 signaling. Phosphatidylserine receptor brain-specific angiogenesis inhibitor 1 (BAI1)-Rac1 signaling, which facilitated efferocytosis by CAFs, participated in crosstalk with Notch1 signaling for optimal production of WISP-1. In addition, a single injection of ApoSQ enhanced WISP-1 production, suppressed the expression of CAF activation markers in isolated Thy1+ CAFs, and inhibited lung metastasis in syngeneic immunocompetent mice via Notch1 signaling. Treatment with CM from CAFs exposed to ApoSQ suppressed tumor growth and lung metastasis, whereas treatment with WISP-1-immunodepleted CM from CAFs exposed to ApoSQ reversed the antitumorigenic and antimetastatic effects. Therefore, treatment with CM from CAFs exposed to apoptotic lung cancer cells could be therapeutically applied to suppress CAF activation, thereby preventing cancer progression and metastasis.

IntroductionGrowth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process. However, the molecular mechanisms regulating neurodegeneration and synaptic plasticity underlying the pathogenesis and progression of Alzheimer's disease (AD) still remain incompletely understood.MethodsRemarkably, the expressions of GAP-43 and BDNF perfectly match in various neurons in the Human Brain Atlas database. Moreover, GAP-43 and BDNF are highly expressed in a healthy adults' hippocampus brain region and are inversely correlated with the amyloid beta (Aβ), which is the pathological peptide of amyloid plaques found in the brains of patients with AD.ResultsThese data led us to investigate the impact of the direct molecular interaction between GAP-43 and BDNF in hippocampal neuron fate. In this study, we show that GAP-43 and BDNF are inversely associated with pathological molecules for AD (Tau and Aβ). In addition, we define the three-dimensional protein structure for GAP-43 and BDNF, including the predictive direct binding sites via analysis using ClusPro 2.0, and demonstrate that the deprivation of GAP-43 and BDNF triggers hippocampal neuronal death and memory dysfunction, employing the GAP-43 or BDNF knock-down cellular models and 5XFAD mice.ConclusionThese results show that GAP-43 and BDNF are direct binding partners in hippocampal neurons and that their molecular signaling might be potential therapeutic targets for AD.

The purpose of this study was to analyze the Korean medicine treatment methods for Postherpetic Neuralgia (PHN) in Korea. There were 5 online databases searched (OASIS, NDSL, RISS, KISS and KMBASE) for studies which were related to PHN. A total of 12 studies were selected. Various treatments such as acupuncture, herbal medicine, and moxibustion were reported treatments for PHN, some of which included Western medicine and Korean medicine treatment. Korean herbal medicine was the most frequently used treatment method, followed by manual acupuncture. Sipjeondaebotanggami was the most frequently used prescription. Poria Sclerotium was the most frequently used principal herb, followed by Angelicae Gigantis Radix, Zingiberis Rhizoma, and Ginseng Radix. GB44, LI4, LR3 were the common acupoints used for the treatment of PHN. CV12 was the most frequently used moxibustion point, and gabapentin was the most frequently used concomitant Western drug. Additional research on Korean medicine treatment of PHN is expected in the future.

Flower shape is a key trait of ornamental and commercial importance in breeding programs for chrysanthemum (Chrysanthemum morifolium Ramat.). Understanding the genetic basis of the phenotypic variation seen in inflorescence-related traits will contribute to genetic improvement and to the development of new varieties. In this study, we investigated the genetic determinants of inflorescence traits using an F1 segregating population derived from a cross between two cultivars with different inflorescence types, ‘Puma White’ (anemone-shaped inflorescence) and ‘Dancer’ (single-type inflorescence). Genotyping-by-sequencing identified 26,847 single-nucleotide polymorphisms (SNPs) between 182 F1 progenies and their parents. A genome-wide association study highlighted 17 SNPs mapping to 15 GBS-tags as being significantly associated with three inflorescence traits: flower type, number of ray florets, and disk flower diameter. No single SNP was associated with flower diameter. These SNP-harboring sequences defined ten candidate genes associated with inflorescence traits. We explored the transcript levels for nine of these in flower buds, disk florets and ray florets using publicly available genome and transcriptome data. These results will provide the genetic and genomic foundation to harness important horticultural traits and explore new avenues in chrysanthemum breeding.

Objectives: This study is designed to statistically analyze data of outpatients visiting for recent 3 years. The purpose is to identify tendencies of patients who visit the hospitals before and after COVID-19. Methods: This study retrospectively analyzed the medical records of 452,487 patients who visited to the Daejeon·Cheonan·Cheongju Korean Medicine Hospital of Daejeon University from January 1, 2018 to August 31, 2020. The data is classified according to year, month, gender, age, and visit type. The statistical analysis was performed using IBM SPSS 25.0. Results: The total number of patients decreased in 2020 compared to before 2020, and the number of patients in each hospital also decreased from the previous year. According to the year of each hospital, the difference by year was not statistically significant at Daejeon Hospital, but Cheonan and Cheongju Hospital showed statistical difference. The change in monthly according to the year by hospital has continued to decrease from January to March in 2020, unlike the previous year, which recovered from a decline in March. In the analysis of patients by age, there was no statistically significant difference in the number of patients in the above 60s according to the year, while those under 60s have a tendency to significantly decrease.. Conclusion: We expect that the results of this study will be used as reference materials in analyzing effects of COVID-19 at health care utilization.

Background: The purpose of this study was to statistically analyze the treatment effect and patient satisfaction of traditional Korean medicine, including acupotomy treatment of cervical herniated intervertebral disc. Methods: This was a retrospective study of 22 patients who received traditional Korean medicine including acupotomy treatment amongst all patients diagnosed with cervical herniated intervertebral discs at the Korean Medicine hospital in Daejeon, Korean, from January 01, 2020 to April 30, 2021. The clinical data from patient medical records were statistically analyzed. Results: The Numeric Rating Scale, the European Quality of Life 5 Dimensions, and the European Quality of Life Visual Analogue Scale questionnaire scores were each compared before and after traditional Korean medicine treatment, including acupotomy, showed significantly improved scores after treatment (p < 0.001). Out of a total of 22 patients, 11 rated the treatment “very satisfactory” (50%), 5 “satisfactory” (22.7%), 5 “indifferent” (22.7%), 1 “unsatisfactory” (4.5%), and 0 “very unsatisfactory” (0%). Of the total 22 patients, 17 patients (77.3%) were willing to have further treatment, and 5 patients (22.7%) were not willing. Conclusion: Traditional Korean medicine treatment including acupotomy was an effective treatment for cervical herniated intervertebral discs. To determine the effect of an individual application (e.g., acupotomy) of traditional Korean medicine treatment for cervical herniated intervertebral disc, a prospective, controlled study is needed.

Neuregulin-1 (NRG1) is an epidermal growth factor family member with essential roles in the developing and adult nervous systems. In recent years, establishing evidence has collectively suggested that NRG1 is a new modulator of central nervous system (CNS) injury and disease, with multifaceted roles in neuroprotection, remyelination, neuroinflammation, and other repair mechanisms. NRG1 signaling exerts its effects via the tyrosine kinase receptors ErbB2-ErbB4. The NRG1/ErbB network in CNS pathology and repair has evolved, primarily in recent years. In the present study, we demonstrated that a unilateral microinjection of CoCl

Lysophosphatidic acid (LPA), an intercellular lipid mediator, is increased in the bronchoalveolar fluids of patients with asthma after allergen exposure. LPA administration exaggerates allergic responses, and the type 2 LPA receptor (LPA

Scutellaria baicalensis has long been used in Asian traditional medicine to prevent and treat suppurative dermatitis, allergic diseases, inflammation, hyperlipemia, and arteriosclerosis. Oroxylin A is a flavone present in Scutellaria baicalensis. Because the root extracts of Scutellaria baicalensis have been shown to have anti-dermatitis effects, the authors investigated the effects of oroxylin A on chemically-induced atopic dermatitis (AD) in an in vivo AD model induced by 1-chloro-2,4-dinitrobenzene (CDNB) in BALB/c mice. CDNB-induced skin hypertrophy and accumulation of mast cells in the epidermis and dermis were significantly ameliorated by oroxylin A. Increased serum levels of immunoglobulin E, as well as pro-inflammatory chemokines and cytokines in the skin and lymph nodes were significantly ameliorated by oroxylin A. Suppression of immune responses in the skin and lymph nodes by oroxylin A decreased the symptoms of AD. Thus, these results proved that oroxylin A is an effective component of Scutellaria baicalensis for treating the symptoms of AD.

Background: This study aims to statistically analyze and compare the curative effect and satisfaction level between typical traditional Korean medicine treatment and nonsurgical spinal decompression treatment.Methods: Of the patients who were diagnosed with the cervical or lumbar herniated intervertebral disc at the Department of Acupuncture and Moxibustion Medicine at the Daejeon Korean Medicine Hospital from April 14th to August 25th, 2019, this study retrospectively analyzed the medical records of 31 patients who underwent nonsurgical spinal decompression treatment and traditional Korean medicine (assigned to Group A) and another 31 patients who received typical traditional Korean medicine alone (assigned to Group B). The clinical data were analyzed using IBM SPSS Version 23.0.Results: No statistically significant differences appeared in terms of sociodemographic, condition, and therapeutic characteristics, except whether the patient received Western medicine treatment, before or after a treatment with traditional Korean medicine. Group A exhibited higher variations in numeric rating scale, EuroQol- 5 dimension and EuroQol visual analogue scale scores compared to Group B as determined by independent sample t test and analysis of covariance. In addition, the satisfaction score of Group A was higher than that of Group B The result of cross analysis revealed that desire for continued treatment in Group A was higher than that of Group B.Conclusion: This retrospective observational study showed that the patients with nonsurgical spinal decompression treatment reported a greater reduction in pain, improved quality of life and satisfaction than patients receiving typical traditional Korean medicine.

We constructed a high-speed X-ray projection microscope at beamline 9D of the Pohang Light Source-II (PLS-II). The microscope was able to take X-ray projection micrographs with a submil-lisecond exposure time by using whitebeam X-rays from the PLS-II bending-magnet synchrotron radiation. It also takes advantage of edge enhancement in phase-contrast imaging, which significantly improves the visibility of soft materials and microfluids. Using the microscope, we captured the spreading of a water droplet on a hydrophilic and oleophilic nonwoven membrane at 1,264 frames per second. The computed tomography (CT), which visualized a three-dimensional wooden structure at a spatial resolution of 2.7 µm, took 2.5 s for scanning.

Scutellaria baicalensis has long been used in Asian traditional medicine to prevent and treat suppurative dermatitis, allergic diseases, inflammation, hyperlipemia, and arteriosclerosis. Oroxylin A is a flavone present in Scutellaria baicalensis. Because the root extracts of Scutellaria baicalensis have been shown to have anti-dermatitis effects, the authors investigated the effects of oroxylin A on chemically induced atopic dermatitis (AD) in an in vivo AD model induced by 1-chloro-2,4-dinitrobenzene (CDNB) in BALB/c mice. CDNB-induced skin hypertrophy and accumulation of mast cells in the epidermis and dermis were significantly decreased by oroxylin A. Increased serum levels of immunoglobulin E, as well as pro-inflammatory chemokines and cytokines in the skin and lymph nodes, were significantly decreased by oroxylin A. Suppression of immune responses in the skin and lymph nodes by oroxylin A decreased the symptoms of AD. Thus, these results proved that oroxylin A is an effective component of Scutellaria baicalensis for treating the symptoms of AD.

Background: Suspicion of lesions and prediction of the histology of esophageal cancers or premalignant lesions in endoscopic images are not yet accurate. The local feature selection and optimization functions of the model enabled an accurate analysis of images in deep learning. Objectives: To establish a deep-learning model to diagnose esophageal cancers, precursor lesions, and non-neoplasms using endoscopic images. Additionally, a nationwide prospective multicenter performance verification was conducted to confirm the possibility of real-clinic application. Methods: A total of 5162 white-light endoscopic images were used for the training and internal test of the model classifying esophageal cancers, dysplasias, and non-neoplasms. A no-code deep-learning tool was used for the establishment of the deep-learning model. Prospective multicenter external tests using 836 novel images from five hospitals were conducted. The primary performance metric was the external-test accuracy. An attention map was generated and analyzed to gain the explainability. Results: The established model reached 95.6% (95% confidence interval: 94.2–97.0%) internal-test accuracy (precision: 78.0%, recall: 93.9%, F1 score: 85.2%). Regarding the external tests, the accuracy ranged from 90.0% to 95.8% (overall accuracy: 93.9%). There was no statistical difference in the number of correctly identified the region of interest for the external tests between the expert endoscopist and the established model using attention map analysis (P = 0.11). In terms of the dysplasia subgroup, the number of correctly identified regions of interest was higher in the deep-learning model than in the endoscopist group, although statistically insignificant (P = 0.48). Conclusions: We established a deep-learning model that accurately classifies esophageal cancers, precursor lesions, and non-neoplasms. This model confirmed the potential for generalizability through multicenter external tests and explainability through the attention map analysis.

Background: Oral care reduces the incidence of ventilator-associated pneumonia. In addition, it is important that critically ill patients to maintain their oral health in order to restore their quality of life and to receive adequate nutrition after recovery. Objective: The purpose of this study was to evaluate the effect of professional oral hygiene care (POHC) on the oral health status of patients using a ventilator. Methods: Fifty-seven ventilated trauma patients were admitted to a tertiary medical institution. For 5 days, the dental hygienist performed POHC every 24 h along with routine oral hygiene care (ROHC) every 8 h for the experimental group (Exp.) (n = 29), whereas only ROHC was provided the control group (Cont.) (n = 28). Oral health status was evaluated using a modified bedside oral exam (MBOE). Results: There was no significant difference between the two groups in the total MBOE score up to 48 h after admission. However, the difference between the two groups was significant for MBOE (F = 16.10, p = 0.000), gingiva (F = 6.02, p = 0.018), buccal mucosa (F = 4.21, p = 0.046), and dental plaque score after 72 h (F = 13.15, p = 0.000). Conclusion: This study confirms the importance of POHC in improving the oral health.

Many environmental factors and stresses influence plant growth and development. High salt stress is expected to have a damaging effect on more than 50% of fully arable land by 2050. Understanding the response of plants to excessive use of nitrogen fertilisers and salt stress is vital for increasing crop productivity. However, the effect of excessive nitrate application on plant growth is controversial and not well-understood; therefore, we investigated the effect of a high nitrate supply and high salt stress on plant growth performance. We showed that abi5-7 plants exhibited tolerance to adverse environmental conditions of high nitrate and high salinity stress. Particularly, abi5-7 plants showed lower endogenous nitric oxide levels than Col-0 plants because of their lower nitrate reductase activity, resulting from the decreased transcript levels of NIA2 , a gene encodes nitrate reductase. The supply of excess nitrate reduced the plant's salt stress tolerance, in which nitric oxide appeared to play a crucial role. Therefore, discovering regulators, such as ABI5, that can regulate nitrate reductase activity and understanding the molecular functions of these regulators are important for implementing gene-editing techniques to modulate transcription factor activities, leading to the optimal accumulation of nitric oxide to increase the productivity of crops exposed to various stress environments.

Tianeptine tablets are currently marketed to be designed for immediate-release tablets. The tianeptine has a short half-life, making it difficult to design for sustained-release tablets and achieve bioequivalence with the tianeptine immediate-release tablet (Stablon®). We established the in vitro–in vivo correlation (IVIVC) of three formulations of tianeptine sustained-release tablets according to their granule size. To evaluate sustained drug release, in vitro tests were performed in pH 1.2 media for 24 h. In vivo pharmacokinetic analysis was performed following oral administration of reference drug and test drug to beagle dogs. The dissolution profile revealed delayed release as the size of the granules increased. The dissolution results were confirmed in pharmacokinetic analysis, showing that the half-life was delayed as granule size increased. The final formulation and reference drug showed an equivalent area under the curve (AUC). Through this, IVIVC was established according to the size of the tianeptine sodium granules, which is the purpose of this study, and was used to predict in vivo pharmacokinetics from the formulation composition. This approach may be useful for determining optimal formulation compositions to achieve the desired pharmacokinetics when developing new formulations.

Signal transducer and activator of transcription 6 (STAT6) promotes an anti-inflammatory process by inducing the development of M2 macrophages. We investigated whether modulating STAT6 activity in macrophages using AS1517499, the specific STAT6 inhibitor, affects the restoration of homeostasis after an inflammatory insult by regulating PPARγ expression and activity. Administration of AS1517499 suppressed the enhanced STAT6 phosphorylation and nuclear translocation observed in peritoneal macrophages after zymosan injection. In addition, AS1517499 delayed resolution of acute inflammation as evidenced by enhanced secretion of pro-inflammatory cytokines, reduced secretion of anti-inflammatory cytokines in PLF and supernatants from peritoneal macrophages, and exaggerated neutrophil numbers and total protein levels in PLF. We demonstrate temporal increases in annexin A1 (AnxA1) protein and mRNA levels in peritoneal lavage fluid (PLF), peritoneal macrophages, and spleen in a murine model of zymosan-induced acute peritonitis. In vitro priming of mouse bone marrow-derived macrophages (BMDM) and peritoneal macrophages with AnxA1 induced STAT6 activation with enhanced PPARγ expression and activity. Using AS1517499, we demonstrate that inhibition of STAT6 activation delayed recovery of PPARγ expression and activity, as well as impaired efferocytosis. Taken together, these results suggest that activation of the STAT6 signaling pathway mediates PPARγ expression and activation in macrophages to resolve acute inflammation.

Herpes zoster is a transient disease caused by the reactivation of latent varicella zoster virus. Approximately one in every three people develops herpes zoster during their life time. Postherpetic neuralgia is the most common complication associated with herpes zoster, and it often persists for several years and even for a lifetime despite the pharmacological treatment. A 74-year-old woman experienced severe postherpetic neuralgia on the coccyx and the vulva for 18 months. Authors performed six times of fluoroscopy-guided nerve blocks including pudendal nerve block, ganglion impar block, and L1 transforaminal epidural block. With repeated nerve blocks, her numeric rating scale decreased from 8 to 4, and after 5 months, her pain was controlled only with oral medication. Postherpetic neuralgia might be treated with nerve blocks regardless of its duration.

Face identification is useful for social interactions and its impairment can lead to severe social and mental problems. This ability is also remarkably important in applied settings, including eyewitness identification and ID verification. Several studies have demonstrated the potential of Transcranial Random Noise Stimulation (tRNS) to enhance different cognitive skills. However, research has produced inconclusive results about the effectiveness of tRNS to improve face identification. The present study aims to further explore the effect of tRNS on face identification using an unfamiliar face matching task. Observers firstly received either high-frequency bilateral tRNS or sham stimulation for 20 min. The stimulation targeted occipitotemporal areas, which have been previously involved in face processing. In a subsequent stage, observers were asked to perform an unfamiliar face matching task consisting of unaltered and pixelated face pictures. Compared to the sham stimulation group, the high-frequency tRNS group showed better unfamiliar face matching performance with both unaltered and pixelated faces. Our results show that a single high-frequency tRNS session might suffice to improve face identification abilities. These results have important consequences for the treatment of face recognition disorders, and potential applications in those scenarios whereby the identification of faces is primordial.

Chlorine dioxide (ClO2) has been widely used as an effective disinfectant to control fungal contamination during postharvest crop storage. In this study, Fusarium oxysporum f. sp. batatas SP-f6 from the black rot symptom of sweetpotato was isolated and identified using phylogenetic analysis of elongation factor 1-α gene; we further examined the in vitro and in vivo inhibitory activities of ClO2 gas against the fungus. In the in vitro medium tests, fungal population was significantly inhibited upon increasing the concentration and exposure time. In in vivo tests, spore suspensions were drop-inoculated onto sweetpotato slices, followed by treatment using various ClO2 concentrations and treatment times to assess fungus-induced disease development in the slices. Lesion diameters decreased at the tested ClO2 concentrations over time. When sweetpotato roots were dip-inoculated in spore suspensions prior to treatment with 20 and 40 ppm of ClO2 for 0–60 min, fungal populations significantly decreased at the tested concentrations for 30–60 min. Taken together, these results showed that ClO2 gas can effectively inhibit fungal growth and disease development caused by F. oxysporum f. sp. batatas on sweetpotato. Therefore, ClO2 gas may be used as a sanitizer to control this fungus during postharvest storage of sweetpotato.

OBJECTIVES To investigate registered nurses' awareness and implementation of oral health care in patients who are hospitalized in general wards or intensive care units (ICUs) in South Korea. METHODS This research was performed as a descriptive survey of 149 nurses working in nine general hospitals with at least 100 beds in major Korean cities. RESULTS Approximately half (40.9%) of the survey respondents reported providing oral health care for hospitalized patients but that relevant protocols were not available at most hospitals or wards (89.5%). Nurses working in an ICU were significantly more likely to provide oral health care than those working in general wards (83.9% vs 15.1%; P

The aim of this study was to report on the resorption of herniated nucleus pulposus following acupotomy treatment. Two patients were treated with acupotomy which included integrative Korean Medicine treatment, for either cervical, or lumbar herniated nucleus pulposus. Magnetic Resonance Imaging was used to produce images before and after (several months) treatment. The Numerical Rating Scale scores and Range of Motion were used to assess the patients at admission and discharge. In both cases, substantial resorption of the respective herniated disc was observed in the magnetic resonance images, with a decrease in the Numerical Rating Scale score. Range of Motion improved in 1 case. This study shows that acupotomy treatment may be a clinically effective treatment for herniated nucleus pulposus resorption and pain relief.

This study investigates how the role and interests of the government affect tax avoidance behavior of public institutions. Consistent with Tang, Mo, and Chan (2017), the government has incentives to act as either a controlling shareholder or a tax collector of public institutions. strong incentives of the government as a controlling shareholder (a tax collector) will increase (decrease) tax avoidance of public institutions. The results of the study provide empirical evidence that independent public institutions with the significant level of profit-making business engage in tax avoidance activities to a lesser extent than dependent public institutions with no or minimal levels of profit-making business. The results support the view that Korean government prefers collecting revenue from public institutions than achieving high after-tax profits through tax avoidance. The study also identifies that management-evaluation-based bonus amplifies the suppressing effects of the government on tax avoidance of public institutions. In additional test, this study finds that local public institutions exhibit tax avoidance to a lesser extent than do central public institutions. These results imply higher motivations of local governments to collect taxes from local public institutions to cover financial deficit. A series of robustness tests support our main results.

Nitrogen is one of the most important macro-nutrients for plant growth and crop productivity. The amount of synthetic nitrogen fertilizers supplied to crops has dramatically increased, leading to a notable rise in crop yields. However, excessive nitrogen use has an enormous negative impact on ecosystems and human health through the emission of intense greenhouse gases, such as nitric oxide derived from the nitrate (NO3–) assimilation cascade. Additionally, owing to the development of extensive irrigation in agriculture, crops are known to suffer from high salt stress. The effect of excessive nitrogen fertilizer application has been studied in some crops, but the effect of high nitrate level and salt stress on plant stress tolerance has not been studied in detail. Therefore, in this study we aimed to study the effects of high concentrations of NO3– on salt stress tolerance in Arabidopsis. In addition, since anthocyanin functions as a reactive oxygen species (ROS) scavenger under abiotic stress conditions, we investigated whether enhanced anthocyanin content helps Arabidopsis to withstand higher salt stress levels under high NO3– concentrations by using pap1-D/fls1ko double mutant plants, which accumulate excessive amount of anthocyanin. We found that Col-0 plants are more sensitive to salt stress under high NO3– concentrations. Although both the pap1-D/fls1ko and fls1ko plants accumulated higher anthocyanin levels and radical scavenging activities than Col-0 plants under both normal and salt stress conditions, the fls1ko plants exhibited much better growth than the pap1-D/fls1ko plants. It appears that the enhanced NR activities and transcript levels of NIA1 and NIA2 in pap1-D/fls1ko and fls1ko plants led to an increase in the synthesis of proteins and proline, which increases osmolytes against salt stress. Our results demonstrate that optimal levels of anthocyanin accumulation can enhance growth performance of plants under high NO3– and salt stress conditions.

Lysophosphatidic acid (LPA), an intercellular lipid mediator, is increased in the bronchoalveolar fluids of patients with asthma after allergen exposure. LPA administration exaggerates allergic responses, and the type 2 LPA receptor (LPA2) has been reported as a therapeutic target for asthma. However, results with LPA2 agonist and antagonist along with LPA2 gene deficient mice have been controversial and contradictory. We compared the effects of LPA2 antagonist (H2L5186303) and agonist (GRI977143) in a single experimental protocol of ovalbumin (OVA)-induced allergic asthma by treating drugs before antigen sensitization or challenge. H2L5186303 showed strong suppressive efficacy when administered before OVA sensitization and challenge, such as suppression of airway hyper responsiveness, inflammatory cytokine levels, mucin production, and eosinophil numbers. However, GRI977143 showed significant suppression when administered before an OVA challenge. Increases in eosinophil and lymphocyte counts in the bronchoalveolar lavage fluid, Th2 cytokine levels, inflammatory scores, and mucin production were differentially ameliorated by the two drugs. The results demonstrate the multiple roles of LPA2 in asthmatic responses. We suggest that the development of LPA2 antagonists would achieve better therapeutic efficacy against asthma than agonists.

Background: To investigate the role of CD47 in inflammatory responses in systemic lupus erythematosus (SLE). Methods: Expression of CD47 and signal regulatory protein alpha (SIRPα) by peripheral blood mononuclear cells (PBMCs) and changes in CD47 expression after exposure to SLE serum, healthy control (HC) serum, recombinant interferon (IFN)-α, or tumor necrosis factor (TNF)-α were examined. Human monocytes and THP1 cells were incubated with lipopolysaccharide (LPS), an anti-CD47 antibody, or both. TNF-α production was examined. Sera from SLE patients and HCs were screened to detect autoantibodies specific for CD47. Results: Twenty-five SLE patients and sixteen HCs were enrolled. CD47 expression by monocytes from SLE patients was higher than those from HCs (mean fluorescence intensity ± SD: 815.9 ± 269.4 vs. 511.5 ± 199.4, respectively, p &lt, 0.001). CD47 expression by monocytes correlated with SLE disease activity (Spearman’s rho = 0.467, p = 0.019). IFN-α but not TNF-α, increased CD47 expression. Exposing monocytes to an anti-CD47 antibody plus LPS increased TNF-α production by 21.0 ± 10.9-fold (compared with 7.3 ± 5.5-fold for LPS alone). Finally, levels of autoantibodies against CD47 were higher in SLE patients than in HCs (21.4 ± 7.1 ng/mL vs. 16.1 ± 3.1 ng/mL, respectively, p = 0.02). Anti-CD47 antibody levels did not correlate with disease activity (Spearman’s rho = −0.11, p = 0.759) or CD47 expression on CD14 monocytes (Spearman’s rho = 0.079, p = 0.838) in patients. Conclusions: CD47 expression by monocytes is upregulated in SLE and correlates with disease activity. CD47 contributes to augmented inflammatory responses in SLE. Targeting CD47 might be a novel treatment for SLE.