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The present study aimed to evaluate the antiobesity potential and synergistic effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts, in HFD-induced obese mice. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD + AM, HFD + LE or HFD + ALM16 (50, 100, and 200 mg/kg) daily for 5 weeks. Compared to the ND group, HFD-fed mice showed significant increases in body weight, food efficiency ratio, weights of white adipose tissues, adipocytes size, liver weight, and hepatic steatosis grade. However, ALM16 significantly reduced those increases induced by HFD. Moreover, as compared to the HFD group, the ALM16 group significantly ameliorated serum levels of lipid profiles (TG, TC, HDL, and LDL), adipokines (leptin and adiponectin), and liver damage markers (AST and ALT levels). Notably, ALM16 was more effective than AM or LE alone and had a similar or more potent effect than Garcinia cambogia extracts, as a positive control, at the same dose. These results demonstrate that ALM16 synergistically exerts anti-obesity effects based on complementary interactions between each component. Also, metabolic profiling between each extract and the ALM16 was confirmed by UPLC-QTOF/MS, and the difference was confirmed by relative quantification.

Machine learning is a powerful method for predicting the outcomes of interactions with educational software, such as the grade a student is likely to receive. However, a predicted outcome alone provides little insight regarding how a student's experience should be personalized based on that outcome. In this paper, we explore a generalizable approach for resolving this issue by personalizing learning using explanations of predictions generated via machine learning explainability methods. We tested the approach in a self-guided, self-paced online learning system for college-level introductory statistics topics that provided personalized interventions for encouraging self-regulated learning behaviors. The system used explanations generated by SHAP (SHapley Additive exPlanations) to recommend specific actions for students to take based on features that most negatively influenced predicted learning outcomes; an "expert system" comparison condition provided recommendations based on predefined rules. A randomized controlled trial of 73 participants (37 expert-system condition, 36 explanation condition) revealed similar learning and topic-choosing behavior between conditions, suggesting that XAI-informed interventions facilitated student statistics learning to a similar degree as expert-system interventions.

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Despite the implementation of intensive phosphorus reduction measures, periodic outbreaks of cyanobacterial blooms in large rivers remain a problem in Korea, raising the need for more effective solutions to reduce their occurrence. This study sought to evaluate whether phosphorus or nitrogen limitation is an effective approach to control cyanobacterial (

Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase domain and G2019S, the most prevalent LRRK2 pathogenic mutation, increases its kinase activity. LRRK2 regulates mitochondria morphology and autophagy in neurons. LPS treatment increases LRRK2 protein level and mitochondrial fission in microglia, and down-regulation of LRRK2 expression or inhibition of its kinase activity attenuates microglia activation. Here, we evaluated the direct role of LRRK2 G2019S in mitochondrial dynamics in microglia. Initial observation of microglia in G2019S transgenic mice revealed a decrease in mitochondrial area and shortage of microglial processes compared with their littermates. Next, we elucidated the molecular mechanisms of these phenotypes. Treatment of BV2 cells and primary microglia with LPS enhanced mitochondrial fission and increased Drp1, a mitochondrial fission marker, as previously reported. Importantly, both phenotypes were rescued by treatment with GSK2578215A, a LRRK2 kinase inhibitor. Finally, the protein levels of CD68, an active microglia marker, Drp1 and TNF-α were significantly higher in brain lysates of G2019S transgenic mice compared with the levels in their littermates. Taken together, our data suggest that LRRK2 could promote microglial mitochondrial alteration via Drp1 in a kinase-dependent manner, resulting in stimulation of pro-inflammatory responses. This mechanism in microglia might be a potential target to develop PD therapy since neuroinflammation by active microglia is a major symptom of PD., Graphical Abstract

Trafficking in persons is a complicated crime with various characteristics of criminals, victims, and law enforcement. Scholars and practitioners addressing the subject of trafficking in persons must consider specific characteristics of traffickers, vulnerability of victims, and their unique relationships with authority. Additionally, there is an urgent necessity to investigate determinants of police reports of victims because most victims of trafficking are fearful of filing a report. This article explores and analyses characteristics of victims of trafficking in persons and willingness of filing a police report about their victimization in ASEAN countries. By using 128 trafficking data from the United Nations Office on Drugs and Crime (UNODC), this study examines which characteristics of victims have increased their vulnerability to trafficking and how key elements of trafficking including protective factors and risk factors are associated with attitudes of police filing reports of victims in ASEAN countries. Results based on descriptive statistics and chi-square analysis demonstrated that approximately 50% percent of victims were younger than age 20 and there is a statistical relationship between family recognition of initial contact with traffickers and police report behaviour. Logistic regression analysis revealed that family awareness was a statistically significant factor associated with police report behaviour. Further policy implications concerning effective strategies for encouraging victims to report their criminal victimization of trafficking will be discussed.

Network-Centric Operational Environment(NCOE) service becomes critical in today's military environment network because reusability of service and interaction are being increasingly important as well in business process. However, the refinement of service by semantic similarity and functional similar...

Artificial structures installed in rivers can change the natural physical, physiochemical, and biological characteristics of the rivers. Coliform bacteria are important water quality indicators, related to human health. This study investigated the relationship between coliform bacteria and water quality factors at eight weir stations constructed in the Nakdong River, a major river in South Korea. Fifteen water quality factors were analyzed at these sites from 2012 to 2016 using correlation and multiple regression analyses. The results for all stations confirmed the analytical validity, with high adjusted R2 values of approximately 0.6 and 0.8 on average for total and fecal coliforms, respectively. The results showed influential water quality factors affecting the concentration of coliform bacteria at weir stations. Specifically, total coliforms were mostly affected by organic matter and fecal coliforms were mostly affected by phosphate phosphorus and suspended solids. Rainfall was the most influential factor affecting both coliforms. Further, both coliforms were negatively affected by organic matter below the Dalseong weir in the mid- to downstream area of the Nakdong River. A positive relationship with phosphate phosphorus was indicated at all weir stations. To the authors&rsquo, knowledge, this kind of study has never been attempted so far. Thus, the study results can provide important information on influential water quality factors related to coliform bacteria, especially in the Nakdong River, creating a foundation for future water quality management.

This article introduces the history and the long-term goals of the Korea Brain Initiative, which is centered on deciphering the brain functions and mechanisms that mediate the integration and control of brain functions that underlie decision-making. The goal of this initiative is the mapping of a functional connectome with searchable, multi-dimensional, and information-integrated features. The project also includes the development of novel technologies and neuro-tools for integrated brain mapping. Beyond the scientific goals this grand endeavor will ultimately have socioeconomic ramifications that not only facilitate global collaboration in the neuroscience community, but also develop various brain science-related industrial and medical innovations.

Purpose To elucidate the brain's intrinsic response to injury, we tracked the response of neural stem/progenitor cells (NSPCs) located in ventricular-subventricular zone (V-SVZ) to hypoxic-ischemic brain injury (HI). We also evaluated whether transduction of V-SVZ NSPCs with neurogenic factor NeuroD1 could enhance their neurogenesis in HI. Materials and methods Unilateral HI was induced in ICR neonatal mice. To label proliferative V-SVZ NSPCs in response to HI, bromodeoxyuridine (BrdU) and retroviral particles encoding LacZ or NeuroD1/GFP were injected. The cellular responses of NSPCs were analyzed by immunohistochemistry. Results Unilateral HI increased the number of BrdU+ newly-born cells in the V-SVZ ipsilateral to the lesion while injury reduced the number of newly-born cells reaching the ipsilateral olfactory bulb, which is the programmed destination of migratory V-SVZ NSPCs in the intact brain. These newly-born cells were directed from this pathway towards the lesions. HI significantly increased the number of newly-born cells in the cortex and striatum by the altered migration of V-SVZ cells. Many of these newly-born cells differentiated into active neurons and glia. LacZ-expressing V-SVZ NSPCs also showed extensive migration towards the non-neurogenic regions ipsilateral to the lesion, and expressed the neuronal marker NeuN. NeuroD1+/GFP+ V-SVZ NSPCs almost differentiated into neurons in the peri-infarct regions. Conclusion HI promotes the establishment of a substantial number of new neurons in non-neurogenic regions, suggesting intrinsic repair mechanisms of the brain, by controlling the behavior of endogenous NSPCs. The activation of NeuroD1 expression may improve the therapeutic potential of endogenous NSPCs by increasing their neuronal differentiation in HI.

Purpose This was a methodological study that aimed to develop a measurement scale for aging anxiety among middle-aged women. Methods In this study, construct factors were extracted, and a conceptual framework was established through an extensive literature review and in-depth interviews with middle-aged women. Under the conceptual framework, 44 preliminary items were constructed, and a preliminary scale of 25 items was completed after two rounds of expert validation and item review. For this study, data were collected from 201 women aged 40~59 years, and the construct validity and reliability of the preliminary scale were verified. Results To verify the construct validity, exploratory factor analysis was conducted. Four factors containing 19 items were extracted. Concurrent validity of the developed scale was verified with Pearson's correlation analysis. The final scale comprised 4 factors ("Social valueless", "Physical weakness", "Concern about changes in appearance", and "Expectations of old age") and 19 items. The Cronbach's α value was .91. Conclusion The scale for measuring aging anxiety in middle-aged women developed in this study validly reflected the peculiarities of aging anxiety in middle-aged women, who experience many physical, emotional, and social changes. The scale can be said to reflect the cultural background, as it reflected real experiences gained through in-depth interviews with middle-aged women.

Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells (NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)–scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC–scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC–scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI., Tissue engineering: Repairing brain and spinal injuries Biodegradable scaffolds seeded with human fetal brain cells can help repair neurological injuries in rodents. A team led by Kook In Park and Il-Shin Lee from the Yonsei University College of Medicine in Seoul, South Korea, created a mesh of plastic fibers that they bathed in neural progenitor cells. Over the course of several days, these cells differentiated into different types of brain cells, including neurons and glia. The researchers implanted these cell-scaffold complexes into the sites of injury in two rodent models: newborn mice with oxygen deprivation to the brain, and adult rats with severed spinal cords. In both cases, the treatment helped the injured tissues heal and improved the neurological or motor function of the animals. The authors suggest these tissue-engineered structures could also help people with brain or spine injuries.

Background FTY720, an analogue of sphingosine-1-phosphate, has shown potential in the treatment of several autoimmune diseases, such as multiple sclerosis, type 1 diabetes and systemic lupus erythematosus. It prevents development or cure of autoimmune diabetes in animal models. Recently, we reported that FTY720 also prevents development of diabetes in db/db mice by β-cell regeneration in vivo. This study investigated the effect of FTY720 on apoptosis in β-cells in db/db mice treated with FTY720 16 weeks. Methods Six week old female db/db mice were divided into control and FTY720 groups. FTY720 (10 mg/kg) was orally administrated daily. Body weights and fasting glucose levels were measured once a week after overnight fasting. After 16 weeks of treatment, oral glucose and insulin tolerance tests were performed, serum insulin levels and insulin contents in pancreas were determined, and then all mice were subjected to physiological and histological analyses. Results FTY720-treated mice showed normal fasting glucose levels, improved glucose tolerance with normal insulin sensitivity and restored β-cell function to produce and secret insulin. Pancreas histology revealed that FTY720 prevented islet damage and preserved β-cell mass by inhibiting apoptosis and increasing β-cell survival in pancreatic islets. Conclusions We concluded that early intervention with FTY720 in db/db mice can prevent development of diabetes through preserving β-cell mass by inhibiting apoptosis and increasing survival of islet β-cells. Copyright © 2012 John Wiley & Sons, Ltd.

Spiro-linked orthogonal bisilole, 2,3,3′4,4′5-hexaphenyl-1,1′-spirobisilole, has been synthesized and characterized. Its crystal structure and optical properties were also investigated. This compound shows high thermal stability and strong bluish-green emission(λmax = 509 nm) with high PL efficiency (55 ± 5%).

Background Alzheimer’s disease (AD) is an inexorable neurodegenerative disease that commonly occurs in the elderly. The cognitive impairment caused by AD is associated with abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells (NSCs) are self-renewing, multipotential cells that differentiate into distinct neural cells. When transplanted into a diseased brain, NSCs repair and replace injured tissues after migration toward and engraftment within lesions. We investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs) that derived from an aborted human fetal telencephalon at 13 weeks of gestation. Cells were transplanted into the cerebral lateral ventricles of neuron-specific enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13 months of age. Results Implanted cells extensively migrated and engrafted, and some differentiated into neuronal and glial cells, although most hNSCs remained immature. The hNSC transplantation improved spatial memory in these mice, which also showed decreased tau phosphorylation and Aβ42 levels and attenuated microgliosis and astrogliosis. The hNSC transplantation reduced tau phosphorylation via Trk-dependent Akt/GSK3β signaling, down-regulated Aβ production through an Akt/GSK3β signaling-mediated decrease in BACE1, and decreased expression of inflammatory mediators through deactivation of microglia that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic plasticity and anti-apoptotic function via trophic supplies. Furthermore, the safety and feasibility of hNSC transplantation are supported. Conclusions These findings demonstrate the hNSC transplantation modulates diverse AD pathologies and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data provide tangible preclinical evidence that human NSC transplantation could be a safe and versatile approach for treating AD patients. Electronic supplementary material The online version of this article (doi:10.1186/s13024-015-0035-6) contains supplementary material, which is available to authorized users.

Additional details of Methods. (DOCX 33 kb)

Sequences of primers used for reverse transcription (RT) and quantitative (q) PCR. (DOCX 25 kb)

List of primary antibodies used in immunohistochemistry (IHC) and western blot (WB). (DOCX 28 kb)

Stormwater runoff is now a major contributor to the pollution of coastal waters in the United States. Public agencies are responding by requiring stormwater monitoring to satisfy the National Pollutant Discharge Elimination System stormwater permit. However, studies to understand the utility of the current programs or to improve their usefulness have not yet been performed. In this paper, we evaluate the land-use-based program, the industrial stormwater permit program, and beach water-quality monitoring in the County of Los Angeles, California, to determine if the results will be helpful to planners and regulators in abating stormwater pollution. The utility of the program has been assessed based on the programs' ability to accurately estimate the emissions for different classes of land use. The land-use program appears successful, while the industrial monitoring program does not. Beach water-quality monitoring suffers from a lack of real-time monitoring techniques. We also provide suggested improvements, such as sampling method and time, and parameter selection.

California's climate, typified by winter and spring precipitation and summer drought, is often called a Mediterranean climate, and creates a long period for pollutant build-up. The initial storms of the winter season usually have higher pollutant concentrations, which is called a seasonal first flush. To investigate the existence of a seasonal first flush, we analyzed four major data sets, collected over the 1999-2000 to 2002-2003 wet seasons. Trends in seasonal loads were quantified by plotting pollutant concentrations or cumulative pollutant load versus cumulative rainfall or cumulative runoff volume. Pollutant concentrations in the first part of the wet season were ranged from 1.2 to 20 times higher than concentrations near the end of the season, and mass emission rates were similarly higher at the beginning of the season. A seasonal first flush existed for most cases and was strongest for organics, minerals and heavy metals except lead. This result suggests that applying treatment Best Management Practices (BMPs) early in the season could remove several times more pollutant mass than randomly timed or uniformly applied BMPs.

Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Multipotent neural progenitor cells (NPCs) with self-renewing capacity have the potential to reduce neuronal loss and improve the compromised environment in the HI brain injury. However, the therapeutic efficacy of neuronal-committed progenitor cells and the underlying mechanisms of recovery are not yet fully understood. Therefore, this study investigated the regenerative ability and action mechanisms of neuronally committed human NPCs (hNPCs) transduced with neurogenin-2 (NEUROG2) in neonatal HI brain injury. NEUROG2- or green fluorescent protein (GFP)-encoding adenoviral vector-transduced hNPCs (NEUROG2- or GFP-NPCs) were transplanted into neonatal mouse brains with HI injury. Grafted NEUROG2-NPCs showed robust dispersion and engraftment, prolonged survival, and neuronal differentiation in HI brain injury. NEUROG2-NPCs significantly improved neurological behaviors, decreased cellular apoptosis, and increased the neurite outgrowth and axonal sprouting in HI brain injury. In contrast, GFP-NPC grafts moderately enhanced axonal extension with limited behavioral recovery. Notably, NEUROG2-NPCs showed increased secretion of multiple factors, such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NTF3), fibroblast growth factor 9 (FGF9), ciliary neurotrophic factor (CNTF), and thrombospondins 1 and 2 (THBS 1/2), which promoted SH-SY5Y neuroblastoma cell survival and neurite outgrowth. Thus, we postulate that NEUROG2-expressing human NPCs facilitate functional recovery after neonatal HI brain injury via their ability to secrete multiple factors that enhance neuronal survival and neuroplasticity.

Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed.

FTY720, an analogue of sphingosine-1-phosphate, has shown potential in the treatment of several autoimmune diseases, such as multiple sclerosis, type 1 diabetes and systemic lupus erythematosus. It prevents development or cure of autoimmune diabetes in animal models. Recently, we reported that FTY720 also prevents development of diabetes in db/db mice by β-cell regeneration in vivo. This study investigated the effect of FTY720 on apoptosis in β-cells in db/db mice treated with FTY720 16 weeks.Six week old female db/db mice were divided into control and FTY720 groups. FTY720 (10 mg/kg) was orally administrated daily. Body weights and fasting glucose levels were measured once a week after overnight fasting. After 16 weeks of treatment, oral glucose and insulin tolerance tests were performed, serum insulin levels and insulin contents in pancreas were determined, and then all mice were subjected to physiological and histological analyses.FTY720-treated mice showed normal fasting glucose levels, improved glucose tolerance with normal insulin sensitivity and restored β-cell function to produce and secret insulin. Pancreas histology revealed that FTY720 prevented islet damage and preserved β-cell mass by inhibiting apoptosis and increasing β-cell survival in pancreatic islets.We concluded that early intervention with FTY720 in db/db mice can prevent development of diabetes through preserving β-cell mass by inhibiting apoptosis and increasing survival of islet β-cells.

Stormwater runoff is now the leading source of water pollution in the United States, and stormwater monitoring programs have only recently been developed. This paper evaluates several stormwater monitoring programs to identify ways of increasing the likelihood of identification of high-risk dischargers and increasing data reliability for assisting in the development of total maximum daily loads. No relationship was found between various types of industrial activity or landuse and water quality data. Stormwater data collected with grab samples has much greater pollutant concentration variability than in potable water or wastewater monitoring programs. Industrial land use is an important source of metals. For grab samples, sampling time during the storm event will affect results. Data from California, which has distinct dry periods, showed a seasonal first flush, whereas data from areas with more uniform rainfall throughout the year did not show a seasonal first flush. Selecting a subset of sites from each monitored category using a flow-weighted composite sampler is an alternative strategy, and may result in lower overall cost with improved accuracy and variability in mass emissions, but may not be less successful in identifying high-risk dischargers.