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Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1β without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1β signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.

산화적 스트레스는 신경퇴행성 질환 발병의 원인으로 알려져 있다. 본 연구는 대표적인 감초 종류인 Glycyrrhiza glabra, G. uralensis와 신품종 감초인 신원감(SW)의 in vitro free radical 소거능을 통한 항산화 활성과 H2O2 유도 산화적 스트레스에 대한 C6 glial cell 보호 효능을 확인하고자 하였다. In vitro assay에서 G. uralensis, G. glabra, SW 추출물은 농도유의적으로 2,2-diphenyl-1-picrylhydrazyl, ·OH, O2- radical 소거능이 증가하여 in vitro 항산화 활성을 확인하였다. 또한, SW 추출물은 G. uralensis, G. glabra 추출물에 비해 총 페놀 및 플라보노이드 함량이 가장 우수하였다. H2O2로 산화적 스트레스를 유도한 C6 glial cell에 3가지 감초 추출물을 각각 처리 시, 농도의존적으로 세포 생존율이 증가와 reactive oxygen species 소거능이 증가하여 3가지 감초 추출물의 산화적 손상에 대한 신경교세포보호 효과를 확인하였다. 특히, SW 추출물은 G. uralensis, G. glabra 추출물에 비해 우수하게 C6 glial cell 보호 효과를 나타내었다. 또한, 3가지 감초 추출물의 신경교세포 보호 메커니즘을 확인하기 위해, 염증 관련 단백질 발현을 측정하였다. 3가지 감초 추출물은 H2O2만을 처리한 control군에 비해 inducible nitric oxide synthase 및 cyclooxygenase-2 발현 감소를 통해 염증반응 조절을 통한 신경교세포 보호 작용기전을 확인하였다. 본 연구는 G. uralensis, G. glabra, SW 등 3가지 감초 추출물이 산화적 손상이 유도된 신경교세포 보호에 유용한 소재로써의 가능성이 있는 것으로 사료된다.

Objectives : The use of risky and persistent organochlorine pesticides was prohibited, but is still detected in many agricultural lands. In this study, Phanerochaete chrysosporium Y-2 (KCCM-10725P) and Streptomyces sp. MJM14747 (KACC 81078BP), which were finally selected among various candidate microorganisms, were applied to field soil and estimated the endosulfan removal rate.Methods : The field testing sites were set to an area of 3 m × 3 m, respectively. A 35% endosulfan emulsion was sprayed on both sites so that the final concentration was about 20 µg/g. Thereafter, 12 kg of original sawdust and 12 kg of sawdust loaded with microbial consortia were mixed at each of the two sites. During the test period for a total of 100 days, samples were taken every 30 days. Soil samples were extracted according to the QuEChERS AOAC method and analyzed by gas chromatography.Results and Discussion : The concentrations immediately after endosulfan emulsion treatment at both sites were detected as 21.2 µg/g and 21.9 µg/g, respectively. The removal rate of endosulfan at the site without microbial consortia treatment (Control) was about 21.9% until the 30th day, and 54.4% on the 100th day. On the other hand, the endosulfan removal rate on the 100th day of the site treated with microbial consortia was 89.5%, which was 1.6 times higher than that of the control site. On the 30th day, the removal rate was 56.8%, and the rate of degradation of endosulfan increased thereafter. Among the major components of endosulfan, the removal rate of α-endosulfan was higher than that of β-endosulfan. After 100 days, the removal rates of α-endosulfan and β-endosulfan were 98.0% and 83.5%, respectively.Conclusions : Streptomyces sp. MJM14747 showed good degradation ability in the presence of endosulfan at a high concentration of around 100 µg/g. Moreover, Phanerochaete chrysosporium Y-2 has a good performance in the removal of β-endosulfan, which is slow degrading components of endosulfan. Microbial consortia are expected to be applied not only to domestic and foreign agricultural land but also to overall bioremediation projects.

Objectives:The use of risky and persistent organochlorine pesticides was prohibited, but is still detected in many agricultural lands. In this study, Phanerochaete chrysosporium Y-2 (KCCM-10725P) and Streptomyces sp. MJM14747 (KACC 81078BP), which were finally selected among various candidate microorganisms, were applied to field soil and estimated the endosulfan removal rate. Methods:The field testing sites were set to an area of 3 m × 3 m, respectively. A 35% endosulfan emulsion was sprayed on both sites so that the final concentration was about 20 µg/g. Thereafter, 12 kg of original sawdust and 12 kg of sawdust loaded with microbial consortia were mixed at each of the two sites. During the test period for a total of 100 days, samples were taken every 30 days. Soil samples were extracted according to the QuEChERS AOAC method and analyzed by gas chromatography. Results and Discussion:The concentrations immediately after endosulfan emulsion treatment at both sites were detected as 21.2 µg/g and 21.9 µg/g, respectively. The removal rate of endosulfan at the site without microbial consortia treatment (Control) was about 21.9% until the 30th day, and 54.4% on the 100th day. On the other hand, the endosulfan removal rate on the 100th day of the site treated with microbial consortia was 89.5%, which was 1.6 times higher than that of the control site. On the 30th day, the removal rate was 56.8%, and the rate of degradation of endosulfan increased thereafter. Among the major components of endosulfan, the removal rate of α-endosulfan was higher than that of β-endosulfan. After 100 days, the removal rates of α-endosulfan and β-endosulfan were 98.0% and 83.5%, respectively. Conclusions:Streptomyces sp. MJM14747 showed good degradation ability in the presence of endosulfan at a high concentration of around 100 µg/g. Moreover, Phanerochaete chrysosporium Y-2 has a good performance in the removal of β-endosulfan, which is slow degrading components of endosulfan. Microbial consortia are expected to be applied not only to domestic and foreign agricultural land but also to overall bioremediation projects.

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease characterized by structural deterioration of the aorta caused by inflammation and oxidative stress, leading to aortic dilatation and rupture. Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, has been reported as a potential negative regulator of inflammatory vascular diseases, and it has been identified as a protein that is increased in patients with ruptured AAA compared to patients with nonruptured AAA. In this study, we demonstrated that PRDX2 was a pivotal factor involved in the inhibition of AAA progression. PRDX2 levels were increased in AAA compared with those in normal aortas in both humans and mice. Ultrasound imaging revealed that the loss of PRDX2 accelerated the development of AAA in the early stages and increased AAA incidence in mice infused with angiotensin II (Ang II). Prdx2−/− mice infused with Ang II exhibited increased aortic dilatation and maximal aortic diameter without a change in blood pressure. Structural deterioration of the aortas from Prdx2−/− mice infused with Ang II was associated with increases in the degradation of elastin, oxidative stress, and intramural thrombi caused by microhemorrhages, immature neovessels, and the activation of matrix metalloproteinases compared to that observed in controls. Moreover, an increase in inflammatory responses, including the production of cell adhesion molecules and the accumulation of inflammatory cells and proinflammatory cytokines due to PRDX2 deficiency, accelerated Ang II-induced AAA progression. Our data confirm that PRDX2 plays a role as a negative regulator of the pathological process of AAA and suggest that increasing PRDX2 activity may be a novel strategy for the prevention and treatment of AAA., Abdominal aortic aneurysm: Potential enzyme biomarker identified An enzyme with antioxidant properties may provide a biomarker and therapeutic agent to help treat abdominal aortic aneurysm (AAA). AAA involves the structural deterioration of the aorta through chronic inflammation and oxidative stress, and can trigger life-threatening artery rupture. An antioxidant enzyme called peroxiredoxin 2 (PRDX2) is increased in patients with ruptures, but whether its role in AAA is beneficial or detrimental is unclear. Goo Taeg Oh at the Ewha Womans University in Seoul, Jong-Gil Park at the Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea, and co-workers examined the effect of PRDX2 on AAA progression. PRDX2 suppressed structural damage in mice, limiting artery dilation and protein degradation. Loss of PRDX2 accelerated AAA development. Measuring levels of PRDX2 may indicate AAA severity in patients, while boosting the enzyme could repair aortic damage.

Aims The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs. Methods and results In human tissues, human umbilical artery ECs, and mouse models for loss of function and gain of function of PTP4A1, we conducted histological analysis, immunostaining, laser-captured microdissection assay, lentiviral infection, small interfering RNA transfection, quantitative real-time PCR and reverse transcription-PCR, as well as luciferase reporter gene and chromatin immunoprecipitation assays. Short hairpin RNA-mediated knockdown of PTP4A1 and overexpression of PTP4A1 in ECs indicated that PTP4A1 is critical for inhibiting the expression of cell adhesion molecules (CAMs). PTP4A1 increased the transcriptional activity of upstream stimulatory factor 1 (USF1) by dephosphorylating its S309 residue and subsequently inducing the transcription of tumour necrosis factor-alpha-induced protein 3 (TNFAIP3/A20) and the inhibition of NF-κB activity. Studies on Ptp4a1 knockout or transgenic mice demonstrated that PTP4A1 potently regulates the interleukin 1β-induced expression of CAMs in vivo. In addition, we verified that PTP4A1 deficiency in apolipoprotein E knockout mice exacerbated high-fat high-cholesterol diet-induced atherogenesis with upregulated expression of CAMs. Conclusion Our data indicate that PTP4A1 is a novel negative regulator of vascular inflammation by inducing USF1/A20 axis-mediated NF-κB inactivation. Therefore, the expression and/or activation of PTP4A1 in ECs might be useful for the treatment of vascular inflammatory diseases.

The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD., Macular degeneration: crucial protein identified A protein found in retinal cells promotes the development of age-related macular degeneration and may provide a therapeutic target. Sight loss through macular degeneration is triggered by disruption to the retinal pigment epithelium (RPE), a layer of cells that carries nutrients to the eye. RPE cells can be disrupted under oxidative stress conditions, but how this influences macular degeneration is unclear. Jeong-Ki Min and Sang-Hyun Lee at the Korea Research Institute of Bioscience and Biotechnology in Daejeon, South Korea, and co-workers found that oxidative stress reduces levels of the thioredoxin-interacting protein (TXNIP) in human RPE cell cultures. This interrupts cellular communication and disturbs the balance between cell proliferation and cell recycling. It also increases the levels of proteins that promote excess blood vessel formation, a key process contributing to macular degeneration.

Rapamycin is well-recognized in the clinical therapeutic intervention for patients with cancer by specifically targeting mammalian target of rapamycin (mTOR) kinase. Rapamycin regulates general autophagy to clear damaged cells. Previously, we identified increased expression of messenger RNA levels of NBR1 (the neighbor of BRCA1 gene; autophagy cargo receptor) in human urothelial cancer (URCa) cells, which were not exhibited in response to rapamycin treatment for cell growth inhibition. Autophagy plays an important role in cellular physiology and offers protection against chemotherapeutic agents as an adaptive response required for maintaining cellular energy. Here, we hypothesized that loss of NBR1 sensitizes human URCa cells to growth inhibition induced by rapamycin treatment, leading to interruption of protective autophagic activation. Also, the potential role of mitochondria in regulating autophagy was tested to clarify the mechanism by which rapamycin induces apoptosis in NBR1-knockdown URCa cells. NBR1-knockdown URCa cells exhibited enhanced sensitivity to rapamycin associated with the suppression of autophagosomal elongation and mitochondrial defects. Loss of NBR1 expression altered the cellular responses to rapamycin treatment, resulting in impaired ATP homeostasis and an increase in reactive oxygen species (ROS). Although rapamycin treatment-induced autophagy by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in NBR1-knockdown cells, it did not process the conjugated form of LC3B-II after activation by unc-51 like autophagy-activating kinase 1 (ULK1). NBR1-knockdown URCa cells exhibited rather profound mitochondrial dysfunctions in response to rapamycin treatment as evidenced by Δψm collapse, ATP depletion, ROS accumulation, and apoptosis activation. Therefore, our findings provide a rationale for rapamycin treatment of NBR1-knockdown human urothelial cancer through the regulation of autophagy and mitochondrial dysfunction by regulating the AMPK/mTOR signaling pathway, indicating that NBR1 can be a potential therapeutic target of human urothelial cancer.

We propose a novel read-in integrated circuit (RIIC) for infrared scene projectors (IRSPs) providing three modes for infrared (IR) scene adaptive operation. Conventional IRSPs have difficulty in simultaneously satisfying IR-scene fidelity-related parameters such as the thermal dynamic range and thermal resolution, since there is a tradeoff between them. To overcome the limitation, a triple-mode RIIC is proposed. A prototype was fabricated using a $0.35~\mu \text{m}$ CMOS process and measurements were performed to determine its performance. The estimated thermal dynamic range varies from 275–385 K to 275–745 K according to the operating mode. Furthermore, the estimated thermal resolution at temperatures below 300 K reaches only up to 30 mK in every mode when using a 12-bit digital-to-analog converter.

Purpose Although Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure and unwanted side effects. Here, we generated genetically modified BCG strains with improved immunotherapeutic effects by adding genes that confer evasion of AMPs. Materials and methods We constructed recombinant BCG (rBCG) strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. Then, the efficacy of the rBCGs was tested in a growth inhibition assay using two bladder cancer cell lines (5637, T24). Results We confirmed the presence of cDNA segments corresponding to the Sic and dltA genes in total mRNA of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA), and these rBCGs showed higher survival against AMPs. The growth inhibitory effects of rBCGs on bladder cancer cells were significantly enhanced compared to those of the parent BCG, and THP-1 migration also increased. After 8 h of infection, the levels of internalization were higher in rBCG-infected bladder cancer cells than in BCG-infected cells, and cells infected with rBCGs showed increased release of antitumor cytokines, such as IL-6/12, TNF-α, and INF-γ, resulting in inhibition of bacterial killing and immune modulation via antimicrobial peptides. Conclusions: rBCG-Sic and rBCG-dltA can effectively evade BCG-stimulated AMPs, and may be significantly improved immunotherapeutic tools to treat bladder cancer.

β-transducin repeats-containing protein-1 (β-TrCP1) serves as the substrate recognition subunit for SCFβ-TrCP E3 ubiquitin ligases, which specifically ubiquitinate phosphorylated substrates. Three variants of β-TrCP1 are known and act as homodimer or heterodimer complexes. Here, we identified a novel full-sequenced variant, β-TrCP1-variant 4, which harbours exon II instead of exon III of variant 1, with no change in the open reading frame. The expression of β-TrCP1-variant 4 is lower than that of variant 1 or 2 in ovarian cancer cell lines, whereas it is abundantly expressed in normal and cancerous ovarian tissues. Moreover, β-TrCP1-variant 2 was aberrantly expressed more than variant 1 in ovarian cancer tissues whereas variant 1 was expressed more in normal tissues. Similar to variants 1 and 2, β-TrCP1-variant 4 directly interacts with β-catenin, one of the substrates of SCFβ-TrCP E3 ubiquitin ligase and down-regulates the transcriptional activity and protein expression of β-catenin with a significantly weaker effect than that by variants 1 and 2. However, the co-expression of β-TrCP1-variant 4 with variant 1 in same proportion has no effect, whereas other combinations effectively down-regulate the activity of β-catenin, indicating that the heterodimer of variants 1 and 4 has no function. Thus, β-TrCP1-variant 4 could play a critical role in SCFβ-TrCP E3 ligase-mediated ubiquitination by acting as a negative regulator of β-TrCP1-variant 1.

Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has significant potential for application in the treatment of urothelial carcinoma (URCa) of the bladder. Previous studies have shown that regulation of the AMP-activated serine/threonine protein kinase (AMPK)-mTOR signaling pathway enhances apoptosis by inducing autophagy or mitophagy in bladder cancer. Alteration of liver kinase B1 (LKB1)-AMPK signaling leads to mitochondrial dysfunction and the accumulation of autophagy-related proteins as a result of mitophagy, resulting in enhanced cell sensitivity to drug treatments. Therefore, we hypothesized that LKB1 deficiency in URCa cells could lead to increased sensitivity to rapamycin by inducing mitochondrial defect-mediated mitophagy. To test this, we established stable LKBI-knockdown URCa cells and analyzed the effects of rapamycin on their growth. Rapamycin enhanced growth inhibition and apoptosis in stable LKB1-knockdown URCa cells and in a xenograft mouse model. In spite of the stable downregulation of LKB1 expression, rapamycin induced AMPK activation in URCa cells, causing loss of the mitochondrial membrane potential, ATP depletion, and ROS accumulation, indicating an alteration of mitochondrial biogenesis. Our findings suggest that the absence of LKB1 can be targeted to induce dysregulated mitochondrial biogenesis by rapamycin treatment in the design of novel therapeutic strategies for bladder cancer.

Background/objectives Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. Materials/methods C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. Results There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B (NFκB) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. Conclusions The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

A 62-year-old man with progressive swelling on his left thigh and leg was referred to the Division of Vascular Surgery. Anticoagulation therapy did not prevent or improve the symptoms of chronic deep vein thrombosis (DVT) from his left external iliac vein to posterior tibial vein. He had no trauma history nor any accidents. He underwent femoral endovenectomy, thrombectomy and stent insertion in left iliac vein. The patient had additional balloon angioplasty for stenosis in left common femoral vein. He had an uneventful postoperative recovery without complication. Leg swelling has been improving and follow-up continues under anticoagulation. We report a case of femoral endovenectomy with iliac stenting, which may be an efficacious treatment for chronic DVT.

Background Sarpogrelate is expected to reduce restenosis by protecting blood vessels from oxidative stress and vascular endothelial dysfunction as well as by acting as an antiplatelet agent after endovascular treatment (EVT). This trial was designed to compare aspirin plus sustained-release (SR) sarpogrelate with aspirin plus clopidogrel for the prevention of restenosis in patients with femoro-popliteal (FP) peripheral artery disease (PAD) who underwent EVT. Methods/Design This is an open label, multicenter, prospective randomized controlled clinical trial. Patients will be eligible for inclusion in this study if they require EVT for stenosis or occlusion of a de novo FP lesion. Patients in each group will receive aspirin 100 mg with clopidogrel 75 mg or aspirin 100 mg with SR sarpogrelate 300 mg (Anplone®) orally once a day for six months. The primary outcome of the study is the restenosis rate, defined as > 50% luminal reduction by computed tomography angiography or catheter angiography in the six-month follow-up period. Secondary outcomes include target lesion revascularization, major bleeding, ipsilateral major amputation, all-cause mortality, and all adverse events that take place in those six months. Discussion This study is a multicenter randomized controlled trial designed to show non-inferiority in terms of the re-stenosis rate of SR sarpogrelate compared to clopidogrel for EVT for PAD in FP lesion patients. Trial registration ClinicalTrials.gov, NCT02959606. Registered on 9 November 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2155-5) contains supplementary material, which is available to authorized users.

Colony stimulating factor 1 receptor (CSF-1R) regulates the monocyte/macrophage system, which is an essential component of cancer development. Therefore, CSF-1R might be an effective target for anti-cancer therapy. The overexpression of transforming growth factor (TGF)-β stimulated clone-22 (TSC-22) inhibits cancer cell proliferation and induces apoptosis, and TSC-22 is emerging as a key factor in tumorigenesis. In this study, we discovered CSF-1R as a new interacting partner of TSC-22 and identified its elevated expression in cervical cancer cells. In particular, we found that TSC-22 interacted with the intracellular tyrosine kinase insert domain (539-749) of CSF-1R, which activates the AKT and ERK signaling pathways. This binding blocked AKT and ERK signaling, thereby suppressing the transcriptional activity of NF-κB. The overexpression of TSC-22 significantly decreased CSF-1R protein levels, affecting their autocrine loop. TSC-22 injected into a xenograft mouse model of human cervical cancer markedly inhibited tumor growth. The reduction of CSF-1R protein significantly suppresses cervical cancer cell proliferation and motility and induces apoptotic cell death. This association between TSC-22 and CSF-1R could be used as a novel therapeutic target and prognostic marker for cervical cancer.

A 71-year-old woman presented with an enlarging mass in the right buttock, with pain and tingling sensation in sitting position. Five years ago, she was diagnosed with acute limb ischemia due to acute thrombosis of right persistent sciatic artery (PSA), and she underwent successful thromboembolectomy and femoro-tibioperoneal trunk bypass. Computed tomography angiography revealed a huge PSA aneurysm (PSAA). During the previous bypass, the distal popliteal artery was ligated just above the distal anastomosis to exclude the PSAA, whose proximal end was already thrombosed. However, PSAA has grown to cause compression symptoms, and the mechanism of aneurysm growth can be ascribed to type 1a or type 2 endoleak. In order to relieve the compression symptoms, aneurysm excision was performed without any injury to the sciatic nerve. A postoperative tingling sensation due to sciatic-nerve stimulation in the supine position resolved spontaneously one month after surgery.

Objective Many depressed adolescents do not seek professional help despite there being evidence-based treatments for depression, such as cognitive behavioral therapy or computer-based therapy. To increase professional help-seeking behavior in depressed adolescents, it is necessary to positively change help-seeking attitudes. This study aimed to explore the effect of sub-groups of help-seeking attitudes, gender, and depression level on adolescents' help-seeking intentions and their perceptions of computer-based psychotherapy. Methods Participants were 246 adolescents aged 13-18 years recruited from six middle and high schools in South Korea. Measures were self-administered questionnaires, and included the Patient Health Questionnaire-9, the Attitudes Toward Seeking Professional Psychological Help Scale, the Intention to Seek Counseling Inventory, Preferences for Depression Treatment, and the Perceptions of Computerized Therapy Questionnaire. Results Help-seeking intentions were positively related with female gender and the recognition of the need for help. A higher level of confidence in therapists was related to high preference for computer-based therapy and face-to-face therapy. Adolescents with more severe depression were more likely to prefer pharmacotherapy. The perceptions of computer-based therapy were more positive in male adolescents, and in adolescents with a higher level of confidence in therapists yet a lower level of interpersonal openness. Conclusion To promote adolescents' help-seeking behavior, improvement of the recognition of the need for help is required, especially among male adolescents. Computer-based therapy provides an alternative for male adolescents with high confidence in therapists yet low interpersonal openness. Consideration of the help-seeking attitudes and gender is needed when providing therapeutic intervention to depressed adolescents.

An estimation of optimal requirement of additional N by cropping pattern and growth stage is very important for greenhouse watermelon. The objectives of this study were to estimate an amount of optimal additional N based on growth, N uptake and yield of watermelon. In order to achieve these goals, we performed the study at farmer’s greenhouse with a fertigation system and watermelon was cultivated three times (spring, summer and autumn) in 2015. The levels of additional N were set up with x0.5, x0.75, x1.0 and x1.5 of the NO₃-N-based soil-testing N supply for watermelon cultivation. The trends of growth and N uptake of watermelon markedly differed from cropping pattern; spring (sigmoid), summer and autumn (linear). The yield of watermelon was the highest at summer season and followed by autumn and spring. Also, the x1.5N showed a significantly higher yield compared to other N treatments. On the basis of growth, N uptake and yield of watermelon, we estimated an optimal level of additional N by cropping pattern and growth stage as follows; 1) spring (transplanting ~ 6 WAT : 6 ~ 14 WAT : 14 ~ harvest = 5 : 90 : 5%), summer (transplanting ~ 4 WAT : 4 ~ 8 WAT : 8 ~ harvest = 25 : 50 : 25%) and autumn (transplanting ~ 4 WAT : 4 ~ harvesting : 50 : 50%). In conclusion, nutrient management, especially N, based on cropping pattern and growth stage was effective for favorable growth and yield of watermelon.

With increasing social concerns for healthy food, the studies on the cultivation of crops to increase accumulation of functional metabolites in crops have been investigated. Accumulation of the metabolites in crops is highly affected by various types of stress, such as nutrient deficiency, water deficit (WD), extreme temperature and UV-B radiation as well as their own life cycle. This review summarizes the previous studies on the effects of environmental stresses, especially WD and UV-B radiation, on accumulation of functional metabolites in crops. UV-B radiation and WD during specific period (mainly at maturation stage) activates the adaptation and/or defense system in crops, thereby increasing biosynthesis of the metabolites. Although WD and UV-B radiation tend to decrease in crop yield, the decrease can be compensated by the production of high value crops having high content of functional metabolites.

Background: Epidural neuroplasty using a Racz catheter has a therapeutic effect. Studies have found no correlation between foraminal stenosis and the outcome of epidural neuroplasty, which is thought to depend on contrast runoff. Objective: To examine the correlation between the contrast spread pattern and pain reduction in cervical epidural neuroplasty using a Racz catheter. Study Design: Retrospective study. Setting: An interventional pain-management practice in a university hospital. Methods: Fluoroscopic images were reviewed retrospectively. The spread of contrast from the neural foramen to a nerve root was called contrast runoff. If the contrast did not spread in this manner, then there was no contrast runoff. We defined successful epidural neuroplasty as a 50% or greater reduction from the pre-procedure numeric rating scale (NRS) score for total pain, and an at least 40% reduction in the neck pain and disability scale (NPDS) score. Results: This study reviewed 169 patients. Among the patients who had a contrast runoff pattern, the epidural neuroplasty was rated as successful in 96 (74.4%), 97 (75.2%), 86 (66.7%), and 79 (61.2%) cases one, 3, 6, and 12 months after the procedure, respectively. When there was no contrast runoff, the epidural neuroplasty was successful in 12 (30%), 12 (30%), 10 (25%), and 10 (25%) cases at one, 3, 6, and 12 months after the procedure (P < 0.001). Logistic regression of the contrast spread pattern and predicting successful epidural neuroplasty gave similar results. Patients with a contrast runoff pattern had odds ratios of 6.788, 7.073, 6.000, and 4.740 at one, 3, 6, and 12 months, respectively (P < 0.001). Limitations: This study lacked a control group, and the patients were not classified by their diagnosed disease, such as spinal stenosis, herniated nucleus pulposus, and post-spinal surgery syndrome. Conclusions: Cervical epidural neuroplasty with a contrast runoff pattern had a higher success rate. Contrast runoff should be observed during neuroplasty, even in the presence of foraminal stenosis. Key words: Cervical spinal pain, contrast, contrast runoff, epidural neuroplasty, percutaneous adhesiolysis, Racz catheter

Endovascular abdominal aortic aneurysm (AAA) repair has been widely used for the treatment of AAA as a safe and efficient method, but endoleaks causing persistent expansion of aneurysm sac may cause aneurysmal rupture and death. Type 3 endoleak is rare but a predominant cause of late rupture. Type 3b endoleak can be misdiagnosed as type 2 endoleak, which is more frequent. Here we report two cases of type 3b endoleak mimicking type 2 endoleak, which were successfully treated by open surgery of partial explantation of the stent-graft and endoaneurysmal interposition graft replacement.

Exposure to fine particulate matter (PM) with diameter

Background Silica nanoparticles (SiNPs) are widely used for biosensing and diagnostics, and for the targeted delivery of therapeutic agents. Safety concerns about the biomedical and clinical applications of SiNPs have been raised, necessitating analysis of the effects of their intrinsic properties, such as sizes, shapes, and surface physicochemical characteristics, on human health to minimize risk in biomedical applications. In particular, SiNP size-associated toxicological effects, and the underlying molecular mechanisms in the vascular endothelium remain unclear. This study aimed to elucidate the detailed mechanisms underlying the cellular response to exposure to trace amounts of SiNPs and to determine applicable size criteria for biomedical application. Methods To clarify whether these SiNP-mediated cytotoxicity due to induction of apoptosis or necrosis, human ECs were treated with SiNPs of four different non-overlapping sizes under low serum-containing condition, stained with annexin V and propidium iodide (PI), and subjected to flow cytometric analysis (FACS). Two types of cell death mechanisms were assessed in terms of production of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress induction, and autophagy activity. Results Spherical SiNPs had a diameter of 21.8 nm; this was further increased to 31.4, 42.9, and 56.7 nm. Hence, we investigated these effects in human endothelial cells (ECs) treated with these nanoparticles under overlap- or agglomerate-free conditions. The 20-nm SiNPs, but not SiNPs of other sizes, significantly induced apoptosis and necrosis. Surprisingly, the two types of cell death occurred independently and through different mechanisms. Apoptotic cell death resulted from ROS-mediated ER stress. Furthermore, autophagy-mediated necrotic cell death was induced through the PI3K/AKT/eNOS signaling axis. Together, the present results indicate that SiNPs within a diameter of

Adipogenesis involved in hypertrophy and hyperplasia of adipocytes is responsible for expanding the mass of adipose tissues in obese individuals. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) are two principal transcription factors induced by delicate signaling pathways, including signal transducer and activator of transcription 5 (STAT5), in adipogenesis. Here, we demonstrated a novel role of ginkgetin, a biflavone from Ginkgo biloba leaves, as a STAT5 inhibitor that blocks the differentiation of preadipocytes into adipocytes. During the differentiation of 3T3-L1 cells, ginkgetin treatment during the first 2 days markedly inhibited the formation of lipid-bearing adipocytes. PPARγ and C/EBPα expression was decreased in 3T3-L1 cells during adipogenesis following ginkgetin treatment, whereas no change was observed in C/EBPβ or C/EBPδ expression. Inhibition of PPARγ and C/EBPα expression by ginkgetin occurred through the prevention of STAT5 activation during the initiation phase of adipogenesis. In addition, ginkgetin-mediated the inhibition of adipogenesis was recapitulated in the differentiation of primary preadipocytes. Lastly, we confirmed the inhibitory effects of ginkgetin on the hypertrophy of white adipose tissues from high-fat diet-fed mice. These results indicate that ginkgetin is a potential anti-adipogenesis and anti-obesity drug.

An estimation of the requirement of minerals based on growth stage and cropping pattern is very important for greenhouse zucchini. This study was performed at farmer’s field which was applied with a fertigation system and a semi-forcing cultivation from Feb. to July in 2014, and nitrogen levels were set up with x0.5, x0.75, x1.0 and x1.5 of the NO₃-N-based soil-testing recommendation for zucchini cultivation. Top dressing of nitrogen (basal : top = 4 : 6) and potassium (basal : top = 3 : 7) was applied with an interval of every two weeks from two and six weeks after transplanting, respectively, and phosphorus was totally supplied with basal dressing. The nitrogen uptake was the order of x1.0, x0.75, x1.5 and x0.5, phosphorus, x1.0, x0.75, x0.5 and x1.5, and potassium, x0.75, x1.0, x1.5 and x0.5. From these results, it was suggested that highest mineral uptake could be reached between x0.75 and x1.0 of the NO₃-N-based soil-testing recommendation. In conclusion, nutrient management based on the growth stage was proven to be better method for favorable growth and yield of zucchini.

This study was conducted to evaluate the effects of reduced nitrogen (N) and potassium (K) fertigation as additional fertilizer on tomato yield and nutrient contents in excessively nutrients-accumulated soil. Shoot and root dry weights (DW), dry matter rate for shoot, root and fruit and number of fruit in both AF50 and AF100 (50 and 100% levels of additional fertilizer) treatments were increased in comparison with those in AF0 (0% level of additional fertilizer) treatment. In case of nutrient uptake by tomato, nitrogen, phosphorous (P) and potassium contents in all tomato parts (leaf, stem, root and fruit) in AF50 and AF100 treatment were lower than those in AF0 treatment. On the contrary, soluble sugar and starch contents in all tomato parts in AF50 and AF100 were higher than those in AF0 treatment. There were differences between AF0 and AF50 or AF100 in tomato growth, yield, nutrient level and contents of soluble sugar and starch. In contrast, the level and initiation point of fertigation did not significantly affect the parameters. Based on our results, the application of properly reduced level of additional fertilizer is possible to maintain the productivity of tomato and alleviate the nutrient accumulation in plastic film house soils.

Both low and high temperatures affect plant growth and development at whole plant level, tissue and even cell level through a variety of metabolic changes. Temperature stress is one of frequently occurring problems in greenhouse crops in summer and winter seasons due to the wide-spread year-round cultivation. In the present study, we investigated the extent of the inhibition of growth, macro-element uptake and soluble carbohydrate production, and the effect of extra-supply of minerals as a means of the recovery from temperature damage. Tomato plants were grown five different growth temperatures (15/8, 20/13, 28/21, 33/23 and 36/26°C), and extra-supply of minerals was composed of 1.5- and 2.0-fold stronger than the standard nutrition (1/2 strength of Hoagland’s solution). Temperature stress significantly adversely affected tomato growth and mineral uptake, whereas soluble carbohydrate accumulation represented temperature-dependent response, more accumulation at low temperature and more consumption at high temperature. The soluble sugars in leaves and stems were mostly declined with the supply of extra-minerals at low and optimal temperatures, whereas remained unchanged at high temperature. The starch levels also remained unchanged or slightly decreased.

BACKGROUND Intraoperative circulatory risk factors are associated with unfavorable outcomes after living donor liver transplantation (LDLT). We investigated whether the preoperative neutrophil-to-lymphocyte ratio (NLR) can predict intraoperative circulatory risks. MATERIAL AND METHODS The perioperative data of 276 patients who underwent LDLT were reviewed retrospectively. The intraoperative circulatory risk score (ICRS) was calculated using the inotropic score, hypotension, blood transfusion, oliguria, and change in serum lactate during LDLT. Perioperative variables including NLRs were compared between the high (≥3.0) and low (

This paper proposes a read-in integrated circuit (RIIC) for infrared scene projectors, which compensates for the voltage drops in ground lines in order to improve the uniformity of the emitter current. A current output digital-to-analog converter is utilized to convert digital scene data into scene data currents. The unit cells in the array receive the scene data current and convert it into data voltage, which simultaneously self-adjusts to account for the voltage drop in the ground line in order to generate the desired emitter current independently of variations in the ground voltage. A 32 × 32 RIIC unit cell array was designed and fabricated using a 0.18-μm CMOS process. The experimental results demonstrate that the proposed RIIC can output a maximum emitter current of 150 μA and compensate for a voltage drop in the ground line of up to 500 mV under a 3.3-V supply. The uniformity of the emitter current is significantly improved compared to that of a conventional RIIC.