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Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

This study investigated the association between children’s perceptions of autonomy support from mothers and teachers in relation to academic procrastination. It also examined the role of self-efficacy for self-regulated learning in mediating these effects. The sample comprised 372 fifth and sixth grade elementary school students from Seoul, Korea. Each completed a questionnaire regarding mothers’ and teachers’ autonomy support, children’s self-regulated learning efficacy, and academic procrastination. The results indicated that whereas mothers’ autonomy support had a direct effect on children’s academic procrastination, teachers’ support did not. In other words, children who perceived higher levels of autonomy support from mothers tended to exhibit less academic procrastination. Regarding indirect paths, children who perceived higher levels of mothers’ and teachers’ autonomy support displayed greater efficacy for selfregulated learning, which corresponded to lower levels of academic procrastination. The discussion highlights the vital roles of autonomy support from mothers and teachers in enhancing children’s feelings of effective self-regulated learning and encouraging them to complete academic tasks. Furthermore, the present study considered not only outward behavioral factors but also the underlying cognitive and affective aspects of delaying behavior that underpin the effects of self-regulated learning efficacy and autonomy support of mothers and teachers on academic procrastination.

Objectives: Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls.Methods: We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated.Results: The nodes with the highest predictability and expected influence in both patients and controls were cognitive (Co) and emotional domains (Em) of the BS and emotional abuse (EMO) of the ETI. The EMO was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative other (NO) and negative self (NS) of the BCSS mediated EMO to other BCSS or BS for patients and controls, respectively.Conclusion: Our findings suggest that rumination and EMO were central symptoms in both groups and that NO and NS played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002

Summary Induced pluripotent stem cells (iPSCs) and cancer cells share cellular similarities and transcriptomic profiles. Here, we show that an iPSC-based cancer vaccine, comprised of autologous iPSCs and CpG, stimulated cytotoxic antitumor CD8+ T cell effector and memory responses, induced cancer-specific humoral immune responses, reduced immunosuppressive CD4+ T regulatory cells, and prevented tumor formation in 75% of pancreatic ductal adenocarcinoma (PDAC) mice. We demonstrate that shared gene expression profiles of “iPSC-cancer signature genes” and others are overexpressed in mouse and human iPSC lines, PDAC cells, and multiple human solid tumor types compared with normal tissues. These results support further studies of iPSC vaccination in PDAC in preclinical and clinical models and in other cancer types that have low mutational burdens., Graphical abstract, Highlights • The iPSC-based cancer vaccine prevents tumor growth in pancreatic cancer • The iPSC-based cancer vaccine induces cytotoxic antitumor T cell and B cell responses • The iPSC-based cancer vaccine reduces immune-suppressive Treg cells • iPSC-cancer signature genes are upregulated in mouse PDAC and human tumors, In this article, Wu and colleagues demonstrate that an iPSC-based cancer vaccine, comprised of iPSCs and CpG, stimulated cytotoxic T cell and B cell responses, reduced immune-suppressive Treg cells, and prevented tumor formation in mice injected with pancreatic ductal adenocarcinoma (PDAC) cells. The “iPSC-cancer signature genes” are overexpressed among iPSC lines, PDAC cells, and multiple human cancers. These results support further studies of iPSC-based cancer vaccine for treatment of PDAC.

Background: South Korea or the Republic of Korea has an area of 100,412.6 km2, and population of 52 million (51,781,000). Methods: Besides our lifetime experiences in receiving training, teaching, and practicing psychiatry, the authors collected information from the literature pertinent to the mental health care in South Korea. This review is intended to familiarize the readers of the Taiwanese Journal of Psychiatry with the information of mental health-care service as well as research and development (R and D) in South Korea. Results: Despite consistent improvement in the overall health status in Korea, the mental health status of the population is low compared with other countries in the Organization for Economic Co-operation and Development (OECD). For example, Korea has the highest suicide-related mortality and more years of life lost due to mental/behavioral diseases, compared to those of the average and a longer-than-average duration of hospital stay, respectively, of the OECD. Conversely, the government has made efforts to overhaul the mental health system. Several remarkable changes have been made in the areas of community-based service, involuntary admission, and unequal treatment. Conclusion: The mental health status is closely associated with the mental health service system, prevalence of mental disorders, health insurance system, admission system, and R and D budget for mental health. To change attitudes related to mental health, strong leadership among mental health professionals is urgently needed.

ObjectiveChronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterize pancreas immune responses using tissues derived from patients with different etiologies of CP and non-CP organ donors in order to identify key signaling molecules associated with human CP.DesignWe performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) and T cell receptor sequencing of pancreatic immune cells isolated from organ donors, hereditary, and idiopathic CP patients who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assay in the second CP patient cohort.ResultsDeep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay.ConclusionSingle-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis that might be leveraged as a potential future target in human hereditary CP.Significance of this studyWhat is already known about this subject?Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease and remains a major source of morbidity among gastrointestinal diseases with no active approved therapy.Inflammation is a known hallmark and contributor to CP pathogenesis. However, little is known about local immune responses in human CP especially with different etiologies.What are the new findings?Single-cell RNA sequencing of pancreatic immune cells from CP patients and organ donors revealed distinct immune transcriptomic features in CP versus non-diseased controls and hereditary versus idiopathic CP.Single-cell T cell receptor sequencing unveiled pancreas-specific clonal expansion in CD8+ T cells and CD4+ T cells-driven unique TCR repertoire changes in hereditary CP.We identified that the CCR6-CCL20 axis was significantly upregulated in hereditary CP compared with controls or idiopathic CP suggesting a potential future target for human hereditary CP.How might it impact on clinical practice in the foreseeable future?The results of this study will improve our understanding of CP heterogeneity and identify distinct immune responses in different types of human CP that could provide novel conceptual directions for therapeutic strategies in treating hereditary and idiopathic CP.The CCR6-CCL20 axis found in hereditary CP could be a potential novel targetable signaling pathways in the treatment of hereditary CP.

G protein-coupled receptor 15 (GPR15) is a chemoattractant receptor which in response to its ligand, C10orf99/GPR15L, promotes colon homing of T cells in health and colitis. The functional role of GPR15 in colon cancer is largely unexplored, motivating our current studies using murine colon cancer models and human colorectal cancer (CRC) tissues. Our initial analysis of human CRC specimen revealed significant reduction in GPR15 expression and frequency of GPR15+immune cells in tumors compared to ‘tumor-free’ surgical margins. In the AOM/DSS murine model of colitis associated colon cancer (CAC), we observed increased colonic polyps/tumor burden and lower survival rate inGpr15-deficient (KO) compared toGpr15-sufficient (Het) mice. Analysis of immune cell infiltrates in the colonic polyps showed significantly decreased CD8+T cells and increased IL-17+CD4+and IL-17+CD8+T cells inGpr15-KO than in Het mice. GPR15 deficiency thus alters the immune environment in colonic polyps to mitigate T cell-mediated anti-tumor responses resulting in severe disease. Consistent with a protective role of GPR15, administration of GPR15L to established tumors in the MC38 CRC mouse model increased CD45+cell infiltration, enhanced TNFαexpression on CD4+and CD8+T cells at the tumor site and dramatically reduced tumor burden. Our findings highlight an important, unidentified role of the GPR15-GPR15L axis in promoting a tumor-suppressive immune microenvironment and unveils a novel, colon-specific therapeutic target for CRC.

ObjectiveChronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterise pancreatic immune responses using tissues derived from patients with different aetiologies of CP and non-CP organ donors in order to identify key signalling molecules associated with human CP.DesignWe performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing and T-cell receptor (TCR) sequencing of pancreatic immune cells isolated from organ donors, hereditary and idiopathic patients with CP who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assays in a second patient with CP cohort.ResultsDeep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T-cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T-cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) expression among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay.ConclusionSingle-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis, a signalling pathway that might be leveraged as a potential future target in human hereditary CP.

The global cosmetic industry is rapidly growing. Brands are seeking growth opportunities and advertising within international markets. However, there is not a clear understanding of effective cosmetic advertising components that may impact consumers' responses. Considering only 18% of claims in advertising are considered trustworthy, consumers may become skeptical towards cosmetic advertisements. The objectives of this study are to test the differences in consumers' trust responses based on advertising factors, the moderating role of ad appeal in this relationship, and the subsequent impact on consumers' purchase behavior. This study selects a US and Korean brand, given the popularity of K-beauty brands within the US market. Result shows that a Korean model is considered more trustworthy to US customers in cosmetic advertisements, on the other hand, a US brand is more trustworthy. The impact of model ethnicity and brand origin on advertising trust differs based on levels of ad appeal.

Objectives Huntington's disease (HD) is a devastating neurodegenerative disease caused by polyglutamine (polyQ) expansion in the huntingtin (HTT) gene. Mutant huntingtin (mHTT) is the main cause of HD and is associated with impaired mitochondrial dynamics, ubiquitin‐proteasome system and autophagy, as well as tauopathy. In this study, we aimed to establish a new neural stem cell line for HD studies. Materials and methods YAC128 mice are a yeast artificial chromosome (YAC)‐based transgenic mouse model of HD. These mice express a full‐length human mutant HTT gene with 128 CAG repeats and exhibit various pathophysiological features of HD. In this study, we isolated a new neural stem cell line from the forebrains of YAC128 mouse embryos (E12.5) and analysed its characteristics using cellular and biochemical methods. Results Compared to wild‐type (WT) NSCs, the YAC128 NSC line exhibited greater proliferation and migration capacity. In addition to mHTT expression, increased intracellular Ca2+ levels and dysfunctional mitochondrial membrane potential were observed in the YAC128 NSCs. YAC128 NSCs had defects in mitochondrial dynamics, including a deficit in mitochondrial axonal transport and unbalanced fusion and fission processes. YAC128 NSCs also displayed decreased voltage response variability and Na+ current amplitude. Additionally, the ubiquitin‐proteasome and autophagy systems were impaired in the YAC128 NSCs. Conclusions We have established a new neural stem line from YAC128 transgenic mice, which may serve as a useful resource for studying HD pathogenesis and drug screening., The YAC128 NSC, a new neural stem cell line derived from the developing forebrain of YAC128 mice, exhibits pathological features of Huntington's disease, including mHTT aggregation, defective ubiquitin and autophagy systems and impaired axonal transport of mitochondria, which can serve as a useful resource for studying HD pathogenesis and drug screening

This study presents a design and evaluation of a mock circulatory platform, which can reproduce blood pressure and its waveforms to provide palpation experience based on the human cardiovascular physiology. To reproduce the human cardiovascular behavior, especially the blood pressure, the proposed platform includes three major modules: heart, artery and reservoir modules. The heart module reproduces source pressure exerted on the whole system with a controlled time-profile. The artery module consists of a resistance valve to adjust the open area of the vessel and a compliance chamber adjusting the wall stiffness of the ascending aorta. The designed platform was cross validated by comparing the theory with a lumped model, i.e., the windkessel model, the measurements from the mock circulatory platform and the real human body data. As a result, the ventricular and aortic pressure waveforms measured from the designed platform were well matched with those of the actual human body. Parametric studies regarding peripheral resistance and aortic compliance were done for the detailed correlation analysis between human cardiovascular physiology and blood pressure. Since the proposed platform is based on the actual cardiovascular physiology, adjusting the structural parameters of the components can reproduce realistic blood pressure waveforms in a controllable manner. This platform is applicable to blood pressure measurement sensor calibration, palpation training, and haptic feedback.

Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease. Despite numerous animal model studies, questions remain about local immune characteristics in human CP. We profiled pancreatic immune cell characteristics in control organ donors and CP patients including those with hereditary and idiopathic CP undergoing total pancreatectomy with islet autotransplantation. Flow cytometric analysis revealed a significant increase in the frequency of CD68(+) macrophages in idiopathic CP. In contrast, hereditary CP samples showed a significant increase in CD3(+) T cell frequency, which prompted us to investigate the T cell receptor β (TCRβ) repertoire in the CP and control groups. TCRβ sequencing revealed a significant increase in TCRβ repertoire diversity and reduced clonality in both CP groups versus controls. Interestingly, we observed differences in Vβ-Jβ gene family usage between hereditary and idiopathic CP and a positive correlation of TCRβ rearrangements with disease severity scores. Immunophenotyping analyses in hereditary and idiopathic CP pancreases indicate differences in innate and adaptive immune responses, which highlights differences in immunopathogenic mechanisms of disease among subtypes of CP. TCR repertoire analysis further suggests a role for specific T cell responses in hereditary versus idiopathic CP pathogenesis, providing insights into immune responses associated with human CP.

최근 알파고의 등장으로 딥러닝 기술에 대한 관심이 고조되고 있다. 딥러닝은 향후 미래의 핵심 기술이 되어 일상생활의 많은 부분을 개선할 것이라는 기대를 받고 있지만, 주요한 성과들이 이미지 인식과 자연어처리 등에 국한되어 있고 전통적인 비즈니스 애널리틱스 문제에의 활용은 미비한 실정이다. 실제로 딥러닝 기술은 Convolutional Neural Network(CNN), Recurrent Neural Network(RNN), Deep Boltzmann Machine (DBM) 등 알고리즘들의 선택, Dropout 기법의 활용여부, 활성 함수의 선정 등 다양한 네트워크 설계 이슈들을 가지고 있다. 따라서 비즈니스 문제에서의 딥러닝 알고리즘 활용은 아직 탐구가 필요한 영역으로 남아있으며, 특히 딥러닝을 현실에 적용했을 때 발생할 수 있는 여러 가지 문제들은 미지수이다. 이에 따라 본 연구에서는 다이렉트 마케팅 응답모델, 고객이탈분석, 대출 위험 분석 등의 주요한 분류 문제인 이진분류에 딥러닝을 적용할 수 있을 것인지 그 가능성을 실험을 통해 확인하였다. 실험에는 어느 포르투갈은행의 텔레마케팅 응답여부에 대한 데이터 집합을 사용하였으며, 전통적인 인공신경망인 Multi-Layer Perceptron, 딥러닝 알고리즘인 CNN과 RNN을 변형한 Long Short-Term Memory, 딥러닝 모형에 많이 활용되는 Dropout 기법 등을 이진 분류 문제에 활용했을 때의 성능을 비교하였다. 실험을 수행한 결과 CNN 알고리즘은 비즈니스 데이터의 이진분류 문제에서도 MLP 모형에 비해 향상된 성능을 보였다. 또한 MLP와 CNN 모두 Dropout을 적용한 모형이 적용하지 않은 모형보다 더 좋은 분류 성능을 보여줌에 따라, Dropout을 적용한 CNN 알고리즘이 이진분류 문제에도 활용될 수 있는 가능성을 확인하였다.

All-trans Retinoic acid (RA) and its derivatives are potent therapeutics for immunological functions including wound repair. However, the molecular mechanism of RA modulation in innate immunity is poorly understood, especially in macrophages. We found that topical application of RA significantly improves wound healing and that RA and IL-4 synergistically activate Arg1, a critical gene for tissue repair, in M2 polarized macrophages. This involves feed forward regulation of Raldh2, a rate-limiting enzyme for RA biosynthesis, and requires Med25 to coordinate RAR, STAT6 and chromatin remodeler, Brg1 to remodel the +1 nucleosome of Arg1 for transcription initiation. By recruiting elongation factor TFIIS, Med25 also facilitates transcriptional initiation-elongation coupling. This study uncovers synergistic activation of Arg1 by RA and IL-4 in M2 macrophages that involves feed forward regulation of RA synthesis and dual functions of Med25 in nucleosome remodeling and transcription initiation-elongation coupling that underlies robust modulatory activity of RA in innate immunity.

Zhang et al recently described ACE2 expression along the GI tract and suggests the digestive system as a potential route for COVID-19.1 ACE2 is also expressed in the pancreas2 and lipase elevations, suggestive of pancreatic involvement, have been reported among patients with COVID-19.3 A recent case report4 demonstrated that severe pancreatitis may occur in COVID-19. However, the clinical implications of these findings with regards to COVID-19 susceptibility among patients with prior pancreatitis are unclear. In this retrospective study, we explored the prevalence, risk factors and outcomes of COVID-19 among patients with a history of pancreatitis. Consecutive patients whose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA testing was performed at Stanford between 4 March 2020, and 14 April 2020 (Institutional Review Board (IRB) protocol 55975) and had a history of acute (K85) or chronic pancreatitis (K86) were included. We performed univariate and multivariate logistic regression to determine …

Nutrient loading is an important aspect of reservoir ecosystems that can be affected by climate change. This study explored the effects of climate change on nutrients in the Juam Dam watershed using the Hydrological Simulation Program-Fortran (HSPF). Eight Global Circulation Models (GCMs) under Representative Concentration Pathways (RCPs) 4.5 and 8.5 were used to investigate the impact of climate change for the 2020s, 2050s, and 2080s. Based on an eight-model ensemble, we observed increasing trends in minimum (maximum) temperature at rates of 0.9, 1.8, and 2.2 (0.9, 1.7, and 2.2) °C/period under RCP 4.5 and of 1.0, 2.4, and 4.1 (1.0, 2.3, and 4.0) °C/period under RCP 8.5. Annual precipitation was predicted to increase by 5.0%, 8.2%, and 10.8% (4.8%, 10.5%, and 19.8%) under RCP 4.5 (RCP 8.5). The consequences of increased rainfall and temperature were reflected in the annual T-N loadings per unit area that were projected to increase by 14.8%, 16.0%, and 23.1% (16.2%, 18.3%, and 31.7%) under RCP 4.5 (RCP 8.5) when compared with historical data (1976–2005). The annual T-P loadings per unit area were projected to increase by 14.8%, 16.4%, and 23.1% (15.5%, 19.3%, and 32.7%) under RCP 4.5 (RCP 8.5). These findings were most evident in subwatersheds with a high ratio of agricultural land.

ANOVA was conducted to determine which ethnicity of model (i.e., Caucasian vs. Korean) is most attractive to U.S. consumers and to determine whether ethnicity has an effect on model evaluations according to skin tone. This study found that Caucasian women, generally, prefer a Caucasian model over three different skin tones when compared to a Korean model. Results also indicate that a medium skin tone had the highest evaluation among the three skin tones.

This study used SEM and found the role of 3D authenticity in mobile apps is to prompt affective as well as cognitive reactions toward mobile shopping in a positive way, instead to minimize possible negative m-shopping aspects like perceived risk.

Background Oral allergy syndrome (OAS) is an immunoglobulin E (IgE)-mediated hypersensitivity that occurs frequently in older children with pollen sensitization. This study focused on the clinical characteristics of OAS in children with atopic dermatitis (AD) and birch sensitization. Method s: A total of 186 patients aged 2–18 years with AD and birch sensitization were enrolled in this study between January 2016 and March 2017. Their levels of serum total IgE and birch- and ragweed-specific IgE (sIgE) were measured using ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden). Information regarding causative foods and symptoms were obtained via interviews. The patients were divided into 3 groups according to their ages (group 1, 2–6 years; group 2, 7–12 years; and group 3, 13–18 years). Results Eighty-one of the 186 (43.5%) children with AD who were sensitized to birch pollen were diagnosed as having OAS. The prevalence of OAS in group 1 (the children who had AD and birch sensitization aged 2–6 years) was 36.6%. A greater predominance of men was noted in the non-OAS group (77.1%) compared to the OAS group (60.5%). Apples were the most common causative food in group 2 and 3 while kiwis were the most common cause of OAS in group 1. There was a statistically significant correlation between birch-sIgE levels and the prevalence of OAS (P = 0.000). The cut-off value was 6.77 kUA/L with 55.6% sensitivity and 79.0% specificity (area under the curve 0.653). Conclusion In our study, the prevalence of OAS in children with AD and birch sensitization was 43.5%. Even in the preschool age group, the prevalence of OAS was considerable. Patients with high levels of birch-sIgE were more likely to have OAS. Clinicians should therefore be vigilant about OAS in patients with a high degree of sensitization to birch pollen and even young children if they have birch sensitization., Graphical Abstract

A modified electrical resistivity survey has been suggested and applied to a leakage detection problem of concrete barrage. We suggest the modified electrical resistivity methods using electrodes floating on the water and apply line current sources instead of conventional point current sources in order to facilitate simple analysis. In addition, the study introduced the following three variations of modified electrode array: Direct potential array, Parallel potential array and Cross potential array. These arrays were tested and investigated through numerical experiment, physical model experiment and geophysical field exploration in order to verify their applicability to the water leakage detection of a concrete barrage. When water leakage occurred, all kind of array operations demonstrated distinct changes of aspects of potential difference in graphs obtained by not only the numerical and physical model experiments but also geophysical field exploration. Therefore, this modified electrode arrays of electrical resistivity survey, which has been adapted to the concrete barrage, has been found to be a useful method to detect water leakage.

Macrophage classical (M1) versus alternative (M2) polarization is critical for the homeostatic control of innate immunity. Uncontrolled macrophage polarization is frequently implicated in diseases. This study reports a new functional role for receptor-interacting protein 140 (RIP140) in regulating this phenotypic switch. RIP140 is required for M1 activation, and its degradation is critical to LPS-induced endotoxin tolerance (ET). Here, we found that failure to establish RIP140 degradation-mediated ET prevents M2 polarization, and reducing RIP140 level facilitates an M1/M2 switch, resulting in more efficient wound healing in animal models generated with either transgenic or bone marrow transplant procedures. The M2-suppressive effect is elicited by a new function of RIP140 that, in macrophages exposed to M2 cues, is exported to cytosol, forming complexes with CAPNS1 (calpain regulatory subunit) to activate calpain 1/2, that activates PTP1B phosphatase. The activated PTP1B then reduces STAT6 phosphorylation, thereby suppressing the efficiency of M2 polarization. It is concluded that RIP140 plays dual roles in regulating the M1-M2 phenotype switch: the first, in the nucleus, is an M1 enhancer and the second, in the cytosol, is an M2 suppressor. Modulating the level and/or subcellular distribution of RIP140 can be a new therapeutic strategy for diseases where inflammatory/anti-inflammatory responses are critical.

Osteolytic bone diseases, such as osteoporosis, are characterized by diminished bone quality and increased fracture risk. The therapeutic challenge remains to maintain bone homeostasis with a balance between osteoclast-mediated resorption and osteoblast-mediated formation. Osteoclasts are formed by the fusion of monocyte/macrophage-derived precursors. Here we report, to our knowledge for the first time, that receptor-interacting protein 140 (RIP140) expression in osteoclast precursors and its protein regulation are crucial for osteoclast differentiation, activity, and coupled bone formation. In mice, monocyte/macrophage-specific knockdown of RIP140 (mϕRIP140KD) resulted in a cancellous osteopenic phenotype with significantly increased bone resorption and reduced bone formation. Osteoclast precursors isolated from mϕRIP140KD mice had significantly increased differentiation potential. Furthermore, conditioned media from mϕRIP140KD primary osteoclast cultures significantly suppressed osteoblast differentiation. This suppressive activity was effectively and rapidly terminated by specific Syk-stimulated RIP140 protein degradation. Mechanistic analysis revealed that RIP140 functions primarily by inhibiting osteoclast differentiation through forming a transcription-suppressor complex with testicular receptor 4 (TR4) to repress osteoclastogenic genes. These data reveal that monocyte/macrophage RIP140/TR4 complexes may serve as a critical transcription regulatory complex maintaining homeostasis of osteoclast differentiation, activity, and coupling with osteoblast formation. Accordingly, we propose a potentially novel therapeutic strategy, specifically targeting osteoclast precursor RIP140 protein in osteolytic bone diseases.