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Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN regulates gastrointestinal motility in tetrapods from amphibians to mammals, recent studies indicate that MLN is not involved in the regulation of isolated intestinal motility in zebrafish, at least in vitro. To determine the unknown function of MLN in teleosts, we examined the expression of MLN and the MLN receptor (MLNR) at the cellular level in Japanese medaka (Oryzias latipes). Quantitative PCR revealed that mln mRNA was limitedly expressed in the gut, whereas mlnr mRNA was not detected in the gut but was expressed in the brain and kidney. By in situ hybridization and immunohistochemistry, mlnr mRNA was detected in the dopaminergic neurons of the area postrema in the brain and the noradrenaline-producing cells in the interrenal gland of the kidney. Furthermore, we observed efferent projections of mlnr-expressing dopaminergic neurons in the lobus vagi (XL) and nucleus motorius nervi vagi (NXm) of the medulla oblongata by establishing a transgenic medaka expressing the enhanced green fluorescence protein driven by the mlnr promoter. The expression of dopamine receptor mRNAs in the XL and cholinergic neurons in NXm was confirmed by in situ hybridization. These results indicate novel sites of MLN activity other than the gastrointestinal tract. MLN may exert central and peripheral actions through the regulation of catecholamine release in medaka., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.2, 1.0, and 5.0 μg/day), DAG (0.2, 1.0, and 5.0 μg/day), or saline (14 μL/day) intracerebroventricularly 4 days before and 3 days after treatment with cisplatin (30 mg/kg). At the end, the anti-apoptotic potentials of ghrelin and DAG were assessed by measuring Bax expression and cytochrome C activity. Neurotransmitter changes in the brain were evaluated using liquid chromatography-mass spectrometry analysis. Ghrelin and DAG reduced cisplatin-induced emesis in the delayed (24-72 h) but not the acute phase (0-24 h) of emesis. Ghrelin also partially reversed the inhibitory effects of cisplatin on food intake without affecting gastrointestinal myoelectrical activity or causing hypothermia; however, ghrelin or DAG did not prevent these effects. Ghrelin and DAG could attenuate the cisplatin-induced upregulation of Bax and cytochrome C in the ileum. Cisplatin dysregulated neurotransmitter levels in the frontal cortex, amygdala, thalamus, hypothalamus, and brainstem, and this was partially restored by low doses of ghrelin and DAG. Our findings suggest that ghrelin and DAG exhibit protective effects against cisplatin-induced delayed emesis. The underlying antiemetic mechanism may involve GHSR and/or unspecified pathways that modulate the neurotransmitters involved in emesis control in the brain and an action to attenuate apoptosis in the gastrointestinal tract., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Glucagon like peptide-1 (GLP-1) is a peptide hormone encoded by the pre-proglucagon gene that serves multiple physiological functions, including incretin action. While GLP-1 is primarily synthesized in the L cells of the lower intestine, recent findings indicate its presence in the stomachs of both rats and humans. However, the role of gastric GLP-1 in other species remains unclear. In this study, we aimed to identify GLP-1-producing cells and examine the localization of GLP-1 production in the mouse stomach. We found that pre-proglucagon mRNA was higher in the corpus than that in the antrum of the stomach. In addition, GLP-1 immunoreactive cells were found in the gastric mucosa, and their cell number was higher in the corpus than that in the antrum. Double immunofluorescence showed that some GLP-1 immunoreactive cells displayed somatostatin immunoreactivity, whereas did not co-localize with ghrelin and gastrin. Moreover, transmembrane G protein-coupled Receptor 5 (TGR5) agonist decreased pre-proglucagon mRNA expression in SG-1 cells in a concentration-dependent manner, and in vivo experiments showed a decrease in its mRNA levels in the gastric corpus but not in the antrum. This study marks the first report of GLP-1 production in the mouse stomach. Our findings suggest that gastric pre-proglucagon mRNA expression is regulated by a distinct mechanism compared to the L cells of the lower intestine., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Motilin is an important hormonal regulator in the migrating motor complex (MMC). Free fatty acid receptor-1 (FFAR1, also known as GPR40) has been reported to stimulate motilin release in human duodenal organoids. However, how FFAR1 regulates gastric motility in vivo is unclear. This study investigated the role of FFAR1 in the regulation of gastric contractions and its possible mechanism of action using Suncus murinus . Firstly, intragastric administration of oleic acid (C18:1, OA), a natural ligand for FFAR1, stimulated phase II-like contractions, followed by phase III-like contractions in the fasted state, and the gastric emptying rate was accelerated. The administration of GW1100, an FFAR1 antagonist, inhibited the effects of OA-induced gastric contractions. Intravenous infusion of a ghrelin receptor antagonist (DLS) or serotonin 4 (5-HT4) receptor antagonist (GR125487) inhibited phase II-like contractions and prolonged the onset of phase III-like contractions induced by OA. MA-2029, a motilin receptor antagonist, delayed the occurrence of phase III-like contractions. In vagotomized suncus, OA did not induce phase II-like contractions. In addition, OA promoted gastric emptying through a vagal pathway during the postprandial period. However, OA did not directly act on the gastric body to induce contractions in vitro . In summary, this study indicates that ghrelin, motilin, 5-HT, and the vagus nerve are involved in the role of FFAR1 regulating MMC. Our findings provide novel evidence for the involvement of nutritional factors in the regulation of gastric motility.

Background: Colonic motility is regulated by various factors along the gut-brain axis; however, detailed mechanisms are unknown. This study aimed to examine the involvement of the autonomic nervous system in colonic motility. Suncus murinus (suncus) is a small laboratory mammal suitable for gastrointestinal motility studies., Methods: Colonic motility and concomitant feeding and defecation behaviors in vagotomized and reserpine-administered suncus were recorded simultaneously for 24 h. Furthermore, we performed immunohistochemistry on tyrosine hydroxylase (TH) and in situ hybridization on corticotropin-releasing hormone (CRH) in suncus brain. Additionally, we examined c-Fos expression in the brain using immunohistochemistry in conscious suncus with colorectal distension., Key Results: In vagotomized suncus, clustered giant migrating contractions (GMCs), consisting of strong contractions occurring in a short time, were observed, and the percentage of GMCs without defecation increased. The frequency of GMCs in the reserpine-administered suncus increased during a light period (ZT0-4, 4-8) and decreased during a dark period (ZT16-20, 20-24) compared to a vehicle group. Additionally, the percentage of GMCs without defecation in the reserpine-administered suncus increased. Suncus TH-immunopositive neurons were found in the locus coeruleus (LC), as shown in rodents. In contrast, CRH mRNA-expressing cells were not observed in a region assumed to be the Barrington's nucleus (Bar). Furthermore, colorectal distension in conscious suncus induced c-Fos expression in LC TH neurons., Conclusions & Inferences: Our results suggest that the vagus and sympathetic nerves are not required for induction of GMCs in vivo. However, they are likely to exert a modulatory role in control of GMC frequency in Suncus murinus., (© 2023 John Wiley & Sons Ltd.)

Composite materials are popular because of their high performance capabilities, but new material development is time-consuming. To accelerate this process, researchers studying material informatics, an academic discipline combining computational science and material science, have developed less time-consuming approaches for predicting possible material combinations. However, these processes remain problematic because some materials are not suited for them. The limitations of specific candidates for new composites may cause potential new material pairs to be overlooked. To solve this problem, we developed a new method to predict possible composite material pairs by considering more materials than previous techniques. We predicted possible material pairs by conducting link predictions of material word co-occurrence networks while assuming that co-occurring material word pairs in scientific papers on composites were reported as composite materials. As a result, we succeeded in predicting the co-occurrence of material words with high specificity. Nodes tended to link to many other words, generating new links in the created co-occurrence material word network; notably, the number of material words co-occurring with graphene increased rapidly. This phenomenon confirmed that graphene is an attractive composite component. We expect our method to contribute to the accelerated development of new composite materials., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ishii et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Studies have indicated that higher numbers of nurses regarding staffing ensure patient safety and a better practice environment. Using citation analysis, this study visualizes the landscape of nurse staffing research over the last two decades to show the overall publication trends, major contributors, and main research topics. We extracted bibliometric information from PubMed from January 2000 to September 2022. After clustering the network, we analyzed each cluster's characteristics by keyword. A total of 2167 papers were considered for analysis, and 14 clusters were created. The analysis showed that the number of papers published per year has been increasing. Researchers from the US, the UK, Canada, Australia, and Belgium have led this field. As the main clusters in nurse staffing research during the past two decades, the following five research settings were identified: nurse outcome and patient outcome research in acute care hospitals, nurse staffing mandate evaluation research, nursing home research, and school nurse research. The first three clusters accounted for more than 80% of the total number of published papers, and this ratio has not changed in the past 20 years. To further develop nurse staffing research globally, evidence from other geographic areas, such as African and Asian countries, and from long-term care or community settings is necessary.

In a fasting gastrointestinal tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occur that comprises of three phases: I, II, and III. Among these, phase III contractions propagate from the stomach to the lower intestine in mammals, including humans, dogs, and Suncus murinus (suncus). Apart from the phase III of MMC propagating from the stomach, during the gastric phase II, small intestine-originated strong contractions propagate to the lower small intestine; however, the mechanism of contractions originating in the small intestine has not been clarified. In this study, we aimed to elucidate the role of cholecystokinin (CCK) in small intestinal motility. Administration of sulfated CCK-8 in phase I induced phase II-like contractions in the small intestine, which lasted for approximately 10-20 min and then returned to the baseline, while no change was observed in the stomach. Contractions of small intestine induced by CCK-8 were abolished by lorglumide, a CCK1 receptor antagonist. Gastrin, a ligand for the CCK2 receptor, evoked strong contractions in the stomach, but did not induce contractions in the small intestine. To examine the effect of endogenous CCK on contractions of small intestinal origin, lorglumide was administered during phase II. However, there was no change in the duodenal motility pattern, and strong contractions of small intestinal origin were not abolished by treatment with lorglumide. These results suggest that exogenous CCK stimulates contractions of small intestine via CCK1 receptors, whereas endogenous CCK is not involved in the strong contractions of small intestinal origin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sustainable supply chain networks are critical to the survival of companies in interconnected business ecosystems. Today's rapidly changing market conditions require firms to restructure their network resources flexibly. In this study, we quantitatively investigated how firms' ability to adapt to the turbulent market depends on the stable maintenance and flexible recombination of inter-firm relationships. Using the proposed quantitative index "metabolism," we measured the micro-level dynamics of the supply chain, which represents each firm's average replacement rate of business partners. We applied this index to longitudinal data on the annual transactions of about 10,000 firms from 2007 to 2016 in the Tohoku region, which was affected by the 2011 earthquake and tsunami. The distribution of metabolism values differed across regions and industries, indicating differences in the adaptive capacity of the corresponding firms. We also found the typical balance between supply chain flexibility and stability for successful companies that have survived in the market for a long time. In other words, the relationship between metabolism and duration was not linear but U-shaped, indicating an appropriate metabolism value for survival. These findings provide a deeper understanding of supply chain strategies for adapting to regional market dynamics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

A scientist's choice of research topic affects the impact of their work and future career. While the disparity between nations in scientific information, funding, and facilities has decreased, scientists on the cutting edge of their fields are not evenly distributed across nations. Here, we quantify relative progress in research topics of a nation from the time-series comparison of reference lists from papers, using 71 million published papers from Scopus. We discover a steady leading-following relationship in research topics between Western nations or Asian city-states and others. Furthermore, we find that a nation's share of information-rich scientists in co-authorship networks correlates highly with that nation's progress in research topics. These results indicate that scientists' relationships continue to dominate scientific evolution in the age of open access to information and explain the failure or success of nations' investments in science., (© 2023. The Author(s).)

Ghrelin is a gut-derived peptide with several physiological functions, including feeding, gastrointestinal motility, and hormonal secretion. Recently, a host defense peptide, liver-expressed antimicrobial peptide-2 (LEAP2), was reported as an endogenous antagonist of growth hormone secretagogue receptor (GHS-R). The physiological relevance of the molecular LEAP2-GHS-R interaction in mammals has been explored; however, studies on non-mammals are limited. Here, we report the identification and functional characterization of ghrelin and its related molecules in Western clawed frog (Xenopus tropicalis), a known model organism. We first identified cDNA encoding X. tropicalis ghrelin and GHS-R. RT-qPCR revealed that ghrelin mRNA expression was most abundant in the stomach. GHS-R mRNA was widely distributed in the brain and peripheral tissues, and a relatively strong signal was observed in the stomach and intestine. In addition, LEAP2 was mainly expressed in intestinal tissues at higher levels than in the liver. In functional analysis, X. tropicalis ghrelin and human ghrelin induced intracellular Ca 2+ mobilization with EC 50 values in the low nanomolar range in CHO-K1 cells expressing X. tropicalis GHS-R. Furthermore, ghrelin-induced GHS-R activation was antagonized with IC 50 values in the nanomolar range by heterologous human LEAP2. We also validated the expression of ghrelin and feeding-related factors under fasting conditions. After 2 days of fasting, no changes in ghrelin mRNA levels were observed in the stomach, but GHS-R mRNA levels were significantly increased, associated with significant downregulation of nucb2. In addition, LEAP2 upregulation was observed in the duodenum. These results provide the first evidence that LEAP2 functions as an antagonist of GHS-R in the anuran amphibian X. tropicalis. It has also been suggested that the ghrelin/GHS-R/LEAP2 system may be involved in energy homeostasis in X. tropicalis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cholecystokinin (CCK) is a peptide hormone mainly secreted by small intestinal endocrine I-cells and functions as a regulator of gallbladder contraction, gastric emptying, gastrointestinal (GI) motility, and satiety. The cellular effects of CCK in these peripheral tissues are predominantly mediated via CCK-A receptors which are found in smooth muscles, enteric neurons, and vagal afferent neurons in humans and animal models. Although various functions of CCK have been reported to be neurally mediated, it can also stimulate contraction via the CCK receptor on the smooth muscle. However, the entire underlying neural and cellular mechanisms involved in CCK-induced GI contractions are not clearly understood. Here, we first determined the cDNA and amino acid sequences of CCK and CCK-A receptor along with the distributions of cck mRNA and CCK-producing cells in house musk shrew (Suncus murinus, the laboratory strain named as suncus) and examined the mechanism of CCK-induced contraction in the GI tract. Mature suncus CCK-8 was identical to other mammalian species tested here, and suncus CCK-A receptor presented high nucleotide and amino acid homology with that of human, dog, mouse, and rat, respectively. Suncus CCK mRNA and CCK-producing cells were found mainly in small intestine and colon. In the organ bath study, CCK-8 induced dose-dependent contractions in the suncus stomach, duodenum, and jejunum, and these contractions were inhibited by atropine and CCK-A receptor antagonist. These results suggest that CCK-8-induced contraction is mediated in the myenteric cholinergic neural network and that CCK-A receptor is partly responsible for CCK-8-induced contractions. This study indicates that suncus is a useful animal model to study the functions of CCK involved in GI motility., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Comprehensive observations of science, technology, and research policy transactions are important for developing an innovation strategy. We propose a new method that combines the academic landscape and matrix analysis to understand the relationships among activities of three aspects of the technological landscape: science, technology, and research policy. First, we divided academic research into 28 knowledge domains by clustering a citation network of scientific papers. Next, we developed a new matrix classifying them into three groups: "mature technology," "intermediate technology," and "emerging technology." The results showed that research domains in "emerging technology" showed a high rate of patent increase, indicating that they were commercializing rapidly. Finally, we identified the group that each country focused on, and this result reflected the countries' research policies. China and Singapore showed high rates, whereas Japan, France, and Germany had low values. This result reflects countries' research policies and implies that specialty research areas differed by country. As above, our research result implies that academia, industry, and government have paid attention to knowledge domains in "emerging technology" and these are important for creating innovation. A supercapacitor, also known as an electric double layer capacitor or ultracapacitor, was selected as an example in our method. This research could help academic researchers, industrial companies, and policymakers in developing innovation strategies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Identifying promising research as early as possible is vital to determine which research deserves investment. Additionally, developing a technology for automatically predicting future research trends is necessary because of increasing digital publications and research fragmentation. In previous studies, many researchers have performed the prediction of scientific indices using specially designed features for each index. However, this does not capture real research trends. It is necessary to develop a more integrated method to capture actual research trends from various directions. Recent deep learning technology integrates different individual models and makes it easier to construct more general-purpose models. The purpose of this paper is to show the possibility of integrating multiple prediction models for scientific indices by network-based representation learning. This paper will conduct predictive analysis of multiple future scientific impacts by embedding a heterogeneous network and showing that a network embedding method is a promising tool for capturing and expressing scientific trends. Experimental results show that the multiple heterogeneous network embedding improved 1.6 points than a single citation network embedding. Experimental results show better results than baseline for the number of indices, including the author h-index, the journal impact factor (JIF), and the Nature Index after three years from publication. These results suggest that distributed representations of a heterogeneous network for scientific papers are the basis for the automatic prediction of scientific trends., Competing Interests: The authors have declared that no competing interests exist.

Hydrogen-associated electron-doping Mottronics for d-band correlated oxides (e.g., VO 2 ) opens up a new paradigm to regulate the electronic functionality via directly manipulating the orbital configuration and occupancy. Nevertheless, the role of hydrogen in the Mottronic transition of VO 2 is yet unclear because opposite orbital reconfigurations toward either the metallic or highly insulating states were both reported. Herein, we demonstrate the root cause for such hydrogen-induced multiple electronic phase transitions by 1 H quantification using nuclear reaction analysis. A low hydrogenation temperature is demonstrated to be vital in achieving a large hydrogen concentration ( n H ≈ 10 22 cm -3 ) that further enhances the t 2g orbital occupancy to trigger electron localizations. In contrast, elevating the hydrogenation temperatures surprisingly reduces n H to ∼10 21 cm -3 but forms more stable metallic H 0.06 VO 2 . This leads to the recognition of a weaker hydrogen interaction that triggers electron localization within VO 2 via Mottronically enhancing the orbital occupancies.

Motilin, a peptide hormone consisting of 22 amino acid residues, was identified in the duodenum of pigs in the 1970s. It is known to induce gastrointestinal contractions during the interdigestive state in mammals. Although the motilin gene has been identified in various animal species, it has not been studied in amphibians. Here, we identified the motilin gene in the Japanese fire bellied newt (Cynops pyrrhogaster), and conducted an analysis of tissue distribution, morphological observations, and physiological experiments. The deduced mature newt motilin comprises 22 amino acid residues, like in mammals and birds. The C-terminus of the newt motilin showed high homology with motilin from other species compared to the N-terminus region, which is considered the bioactive site. Motilin mRNA expression in newts was abundant in the upper small intestine, with notably high motilin mRNA expression found in the pancreas. Motilin-producing cells were found in the mucosal layer of the upper small intestine and existed as two cell types: open-and closed-type cells. Motilin-producing cells in the pancreas were also found to produce insulin but not glucagon. Newt motilin stimulated gastric contractions but not in other parts of the intestines in vitro, and motilin-induced gastric contraction was significantly inhibited by treatment with atropine, a muscarinic acetylcholine receptor antagonist. These results indicate that motilin is also present in amphibians, and that its gastrointestinal contractile effects are conserved in mammals, birds, and amphibians. Additionally, we demonstrated for the first time the existence of pancreatic motilin, suggesting that newt motilin has an additional unknown physiological role., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the fundamental mechanisms of colonic motility in the house musk suncus (Suncus murinus) as an established animal model of gut motility., Methods: To measure gut motility in free-moving conscious suncus, strain gauge force transducers were implanted on the serosa of the colon and gastric body., Key Results: We recorded diurnal changes in colonic motility and observed the relationship between feeding and colonic motility. Giant migrating contractions (GMCs) of the colon were invariably detected during defecation and tended to increase during the dark period, thereby indicating that colonic motility has a circadian rhythm. Given that GMCs in the suncus were observed immediately after feeding during the dark period, we assume the occurrence of a gastrocolic reflex in suncus, similar to that observed in humans and dogs. We also examined the factors that regulate suncus GMCs. Intravenous administration of 5-HT (100 µg/kg), substance P (10 and 100 µg/kg), calcitonin gene-related peptide (10 µg/kg), and α2 adrenergic receptor antagonist yohimbine (0.5, 1, and 3 mg/kg) induced GMC-like contractions, as did intragastric and intracolonic administration of the transient receptor potential vanilloid 1 agonist, capsaicin (1 mg/kg)., Conclusions & Inferences: These results indicate that the fundamental mechanisms of colonic motility in suncus are similar to those in humans and dogs, and we thus propose that suncus could serve as a novel small animal model for studying colonic motility., (© 2021 John Wiley & Sons Ltd.)

Nesfatin-1 is an anorectic peptide expressed in both peripheral tissues and brain areas involved in the regulation of feeding, emotion and emesis. The aim of the present study is to characterize the distribution of NUCB2/nesfatin-1 in Suncus murinus and to investigate the actions of nesfatin-1 to affect gastrointestinal contractility, emesis, food and water intake, and locomotor activity. The deduced amino acid sequence of S. murinus nesfatin-1 using in silico cloning showed high homology with humans and rodents. NUCB2 mRNA was detected throughout the entire brain and in the gastrointestinal tract, including the stomach and gut. Western blot analysis and immunohistochemistry confirmed the expression of nesfatin-1 protein in these regions. The NUCB2 mRNA levels in the hypothalamus, hippocampus and brainstem were significantly decreased, whereas that in the striatum were increased after 24 h starvation compared to ad libitum -fed animals ( p < 0.05). In in vitro studies, nesfatin-1 (0.3-1,000 pM) failed to contract or relax the isolated gastric antrum and intestinal segments. In conscious, freely moving animals, intracerebroventricular administration of nesfatin-1 (1-50 pmol) induced emesis ( p < 0.05) and suppressed 6-h cumulative food intake ( p < 0.05), without affecting the latency to feeding. Nesfatin-1 (25 pmol, i.c.v.) decreased 24-h cumulative food and water intake by 28.3 and 35.4%, respectively ( p < 0.01). No significant differences in locomotor activity were observed. In conclusion, NUCB2/nesfatin-1 might be a potent regulator of feeding and emesis in S. murinus . Further studies are required to elucidate the mechanism of actions of this peptide as a mediator linking the brainstem NUCB2/nesfatin-1 to forebrain system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Cui, Liu, Jiang, Ngan, Sakata, Takemi, Sakai, Lin, Chan and Rudd.)

Ghrelin is a multifunctional gut peptide with a unique structure, which is modified by a medium chain fatty acid at the third serine by ghrelin O-acyl transferase (GOAT). It is well known that the major source of plasma ghrelin is the stomach, but the transcriptional regulation of gastric ghrelin and GOAT is incompletely understood. Here, we studied the involvement of the nuclear receptors REV-ERBα and REV-ERBβ on ghrelin and GOAT gene expression in vivo and in vitro. Reverse-transcriptase polymerase chain reaction analysis showed that REV-ERBα and REV-ERBβ mRNAs were expressed in the stomach and a stomach-derived ghrelin cell line (SG-1 cells). In vivo experiments with mice revealed the circadian rhythm of ghrelin, GOAT, and REV-ERBs. The peak expression of ghrelin and GOAT mRNAs occurred at Zeitgeber time (ZT) 4, whereas that of REV-ERBα and REV-ERBβ was observed at ZT8 and ZT12, respectively. Treatment of SG-1 cells with SR9009, a REV-ERB agonist, led to a significant reduction in ghrelin and GOAT mRNA levels. Overexpression of REV-ERBα and REV-ERBβ decreased ghrelin and GOAT mRNA levels in SG-1 cells. In contrast, small-interfering RNA (siRNA)-mediated double-knockdown of REV-ERBα and REV-ERBβ in SG-1 cells led to the upregulation in the expression of ghrelin and GOAT mRNAs. These results suggest that REV-ERBs suppress ghrelin and GOAT mRNA expression., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pyridoxine (PN), one of the vitamers of vitamin B6, plays an important role in the maintenance of epidermal function and is used to treat acne and rough skin. Clinical studies have revealed that PN deficiency causes skin problems such as seborrheic dermatitis and stomatitis. However, the detailed effects of PN and its mechanism of action in epidermal function are poorly understood. In this study, we examined the effects of PN on epidermal function in normal human epidermal keratinocytes and found that PN specifically causes an increase in the expression of profilaggrin mRNA, among marker genes of terminal epidermal differentiation. In addition, PN treatment caused an increase in the production of filaggrin protein in a concentration-dependent manner. Treatment with P 2x purinoceptor antagonists, namely, pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate and TNP-ATP hydrate, induced an increase in the filaggrin protein levels. Moreover, we showed that elevated filaggrin production induced upon PN treatment was suppressed by ATP (known as P 2x purinoceptor agonist). This study is the first to report that PN causes an increase in filaggrin transcription and production, and these results suggest that PN-induced filaggrin production may be a useful target as a daily care component in atopic dermatitis, wherein filaggrin levels are specifically reduced., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In this paper, we propose a finger-jointing model to describe the possible ultrastructures of cellulose microfibrils based on new observations obtained through heating of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized cellulose nanofibrils (CNFs) in saturated water vapor. We heated the micrometers-long TEMPO-CNFs in saturated water vapor (≥ 120 °C, ≥ 0.2 MPa) and observed a surprising fact that the long TEMPO-CNFs unzipped into short (100 s of nanometers long) fibers. We characterized the heated TEMPO-CNFs using X-ray diffraction (XRD) and observed the XRD patterns were in consistent with Iβ. We observed also jointed ultrastructures on the heated TEMPO-CNFs via high-resolution transmission electron microscopy (HR-TEM). Thus we concluded that cellulose microfibrils are not seamlessly long structures, but serial jointed structures of shorter blocks. Polysaccharide chains of the short blocks organized in Iβ. The jointed region can be either Iα or amorphous, depending on positions and distances among the chains jointed in proximity. Under heating, Iα was not converted into Iβ but was simply destroyed. The jointed structure implies a "working and resting rhythm" in the biosynthesis of cellulose.

Despite the intensive study of the viral spread of fake news in political echo chambers (ECs) on social networking services (SNSs), little is known regarding the underlying structure of the daily information spread in these ECs. Moreover, the effect of SNSs on opinion polarisation is still unclear in terms of pluralistic information access or selective exposure to opinions in an SNS. In this study, we confirmed the steady, highly independent nature of left- and right-leaning ECs, both of which are composed of approximately 250,000 users, from a year-long reply/retweet network of 42 million Japanese Twitter users. We found that both communities have similarly efficient information spreading networks with densely connected and core-periphery structures. Core nodes resonate in the early stages of information cascades, and unilaterally transmit information to peripheral nodes. Each EC has resonant core users who amplify and steadily spread information to a quarter of a million users. In addition, we confirmed the existence of extremely aggressive users of ECs who co-reply/retweet each other. The connection between these users and top influencers suggests that the extreme opinions of the former group affect the entire community through the top influencers.

Purpose of Review: Ghrelin was discovered in 1999; extensive research and clinical studies on ghrelin have been published in the last 20 years. Physiological research on ghrelin ranges from its appetite-stimulating effects to its association with energy homeostasis. The physiological effects of ghrelin in the gastrointestinal tract and its relevance in the pathological conditions of the gastrointestinal tract have gradually become clearer. The purpose of the review is to provide current information on ghrelin cell biology and physiology, particularly in the gastrointestinal tract., Recent Findings: Ghrelin-producing cells in the stomach are characterized as X/A-like cells, but immunohistochemical analyses have revealed co-expression of several secreted proteins and hormones in ghrelin-producing cells such as nesfatin-1, somatostatin, and pancreastatin. Furthermore, the local physiological roles and/or mechanisms of ghrelin in gastrointestinal functions such as gastric motility and inflammation are discussed., Summary: Ghrelin is a brain-gut hormone with a wide range of physiological actions; hence, it is important to understand its effects on the physiological functions of the gastrointestinal tract to elucidate the biological significance of ghrelin., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Under severe calorie restriction (CR), the ghrelin-growth hormone axis in mice is involved in the maintenance of plasma glucose levels. Ghrelin, a stomach-derived acylated peptide, is up-regulated by the sympathetic nerve in the negative energy status. Central corticotrophin-releasing factor receptor (CRF-R) signalling stimulates the sympathetic tone. The present study aimed to examine the effect of central CRF-R signalling on the maintenance of plasma glucose concentrations in severe calorie-restricted mice with the involvement of ghrelin. Intracerebroventricular injections of urocorin-1 and urocorin-2, which are natural ligands for CRF-R1 and CRF-R2, elevated plasma ghrelin concentrations and ghrelin elevation with an i.c.v. injection of urocorin-1 was cancelled by atenolol (β1 adrenergic receptor antagonist) administration. We then established a mice model of 60% CR and found that the administration of [d-Lys3]-GHRP-6 (a ghrelin receptor antagonist) in mice under 60% CR reduced the plasma glucose concentration more compared to the vehicle mice. Similarly, the atenolol injection in mice under 60% CR significantly reduced the plasma glucose concentration, which was rescued by the co-administration of ghrelin. An i.c.v. injection of the alpha helical CRH, a non-selective corticotrophin-releasing factor receptor antagonist, in mice under 60% CR significantly reduced the plasma glucose concentration, although the co-administration of α-helical CRH with ghrelin maintained plasma glucose levels. These results suggest that central CRF-R signalling is involved in the maintenance of plasma glucose levels in mice under severe CR via the sympathetic-ghrelin pathway., (© 2021 British Society for Neuroendocrinology.)

Highly dispersed graphene nanosheets (GNS) are directly integrated into polyurethane sponge for the very first time. Individual GNS with an average thickness of 5 nm were uniformly encapsulated in polyurethane sponge (PUF). Highly durable, flexible, hydrophilic GNS/PUF demonstrated excellent organic dye absorption properties. For a detailed study, we selected typical water-soluble organic dyes such as methylene blue (MB), ethidium bromide (EtBr), eosin Y (EY). The adsorption behavior follows the Langmuir isotherm model indicating strong monolayer chemisorption. Adsorption capacity (μmol/g) of GNS while using in GNS/PUF is 586.8 (MB), 843.1 (EtBr), and 813.3 (EY). Thermodynamic study on the adsorption with three organic dyes using GNS/PUF revealed that the process was spontaneous and exothermic in nature. Additionally, the rate of adsorption is higher and follow the pseudo-second-order kinetic model. The detailed pH-dependent study showed that cationic dyes' adsorption increases with an increase in pH, and anionic dyes follow the opposite trend. The overall results show that the new adsorbent has highly suitable for practical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A novel deodorizer that is capable of selectively eliminating the odorous chemicals, such as ammonia, trimethylamine, hydrogen sulfide and methyl mercaptan, is described. The deodorizer is a nanostructured aerogel by nature, consisting of 2,2-6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized cellulose nanofibrils (CNF), transition metal divalent cations (M 2+ ), and multi-walled carbon nanotubes (CNT) as the constitutive elements. CNF are firstly mixed with M 2+ (M 2+ , in this paper, typifies Ni 2+ , Co 2+ and Cu 2+ ) to form CNF-M 2+ complexes, monodispersed CNT is then mixed to prepare CNT/CNF-M 2+ waterborne slurries; CNT/CNF-M 2+ hybridized aerogels are finally obtained via freezing-drying of the CNT/CNF-M 2+ waterborne slurries. The CNT/CNF-M 2+ aerogels are a foam-like structure consisting of CNF and CNT as backbones and M 2+ as linkers. The aerogels show higher capabilities (in comparison with activated carbon) for selectively adsorbing ammonia, trimethylamine, hydrogen sulfide and methyl mercaptan. Computing simulations suggest a theoretical conclusion that the odorous chemicals are absorbed in a preferring manner of bimolecular absorptions via the M 2+ moieties. The CNT/CNF-M 2+ hybridized aerogels are lightweight, eco-friendly, and easy to produce in industrial scales. Our new finding, as is described in this paper, demonstrates potential applications of the TEMPO-oxidized CNF to the field of deodorizations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Delayed recognition in which innovative discoveries are re-evaluated after a long period has significant implications for scientific progress. The quantitative method to detect delayed recognition is described as the pair of Sleeping Beauty (SB) and its Prince (PR), where SB refers to citation bursts and its PR triggers SB's awakeness calculated based on their citation history. This research provides the methods to extract valid and large SB-PR pairs from a comprehensive Scopus dataset and analyses how PR discovers SB. We prove that the proposed method can extract long-sleep and large-scale SB and its PR best covers the previous multi-disciplinary pairs, which enables to observe delayed recognition. Besides, we show that the high-impact SB-PR pairs extracted by the proposed method are more likely to be located in the same field. This indicates that a hidden SB that your research can awaken may exist closer than you think. On the other hand, although SB-PR pairs are fat-tailed in Beauty Coefficient and more likely to integrate separate fields compared to ordinary citations, it is not possible to predict which citation leads to awake SB using the rarity of citation. There is no easy way to limit the areas where SB-PR pairs occur or detect it early, suggesting that researchers and administrators need to focus on a variety of areas. This research provides comprehensive knowledge about the development of scientific findings that will be evaluated over time., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2021.)

High-performance/low-cost platinum (Pt)-based electrocatalysts have been established by top-coating both sides of a titanium plate with Pt nanoparticles. The average diameter of the Pt nanoparticles used in this study is approximately 100 nm. Three types of Pt top-coated Pt/Ti electrocatalysts, each having different top-coated Pt layer thicknesses, are prepared. Type I is a monolayered Pt top-coated type, in which the thickness of the top-coated Pt layer is approximately 100 nm; Type II is a few-layered type with a top-coated Pt layer thickness of approximately 200 nm, and Type III is a multilayered type with a top-coated Pt layer thickness of approximately 750 nm. The mass loading of Pt is 0.0215 mg cm -2 for Type I, 0.043 mg cm -2 for Type II, and 0.161 mg cm -2 for Type III. The electrocatalytic activities of each type of Pt/Ti electrocatalyst are evaluated through the electrolysis of acidic water and tap water. Type I gives the highest electrocatalytic efficiencies, which are comparable or even better than the electrocatalytic efficiencies of the state-of-the-art commercially available Pt/C electrode and other metal-/carbon-based HER catalysts. For example, in the case of the electrolysis of acidic water at an overpotential of 0.15 V, Type I shows a Tafel slope of 29 mV dec -1 and a current density of 27.5 mA cm -2 . Even in the case of the electrolysis of tap water, Type I gives an HER Faradaic efficiency of 92%. A model of water (H 2 O), hydronium ions (H 3 O + ), and hydroxyl ions (OH - ) properly adsorbing on the Pt (111) facet is proposed to explain the electrocatalytic mechanism. New insights into the distinguishing properties of the resultant electrolyzed hydrogen water (EHW), namely, the healthy beneficial effects of EHW, are also described, and a new concept of storing and carrying reductive hydrogen (H*) by free Pt nanoparticles is proposed.

For research domains such as life sciences, which pursue fundamental scientific understanding and applications intended for immediate use, academic entrepreneurship has played a pivotal role in commercialization. This paper presents an evaluation method of researchers related to user-inspired fundamental research, using global databases of startup finances and academic research papers of "startup readiness." Case studies of startups related to biopharmaceutical research topics suggest that the biopharmaceutical field has rich opportunities stemming from scientific research, commercialization, and entrepreneurship. This evaluation method sorts specific industry segments by which financing activities are active, and by which related growing research topics attract increased academic attention. We constructed networks of author citation and co-authorship from paper citation networks related to research topics in industry segments in the biopharmaceutical domain. Results obtained across all research topics we surveyed demonstrated that authors in the top 10% of degree centrality ranking in both networks are far more likely to be startup participants than other authors. Our computational approach might provide convenient, dynamic, global, and real-time understanding of the "startup readiness" of researchers working with research topics for which academic attention is emerging in actively financed biopharmaceutical fields., (© 2020 The Author(s).)

Conventionally, the importance of nodes in a network has been debated from the viewpoint of the amount of information received by the nodes and its neighbors. While node evaluation based on the adjacency relationship mainly uses local proximity information, the community structure that characterizes the network has hardly been considered. In this study, we propose a new node index that contributes to the understanding of the inter-community structure of a network by combining the measures of link distribution and community relevance. The visualization of node rankings and rank correlations with respect to the attack tolerance of networks demonstrated that the proposed index shows the highest performance in comparison with five previously proposed indexes, suggesting a new way to detect latent mediators in heterogeneous networks.

Prussian blue (PB), an adsorbent for the selective elimination of radioactive cesium from water, is highly versatile due to its unique crystal structure. However, PB crystals quickly decompose in an alkaline solution, generating hazardous cyanide contamination. In this research, the alkaline susceptibility of PB was remedied by incorporating copper sulfate as a protector. A stability assessment was conducted at several environmental conditions, such as high pH and temperatures from 10 °C to 50 °C, in seawater, artificial seawater, and river water. The crystalline and chemical stability of PB in the new class of composite was extremely high, even at a pH value of 11.2, as confirmed using XRD and total cyanide analysis. A comprehensive mechanism study revealed that, at high pH, the copper ions that cover the PB react with hydroxide ions to form copper hydroxide and shielding inner crystals. To decontaminate radioactive cesium, the first step was to immobilize nano PB on a cellulose nanofiber, followed by copper sulfate stabilization. Then, a spongiform adsorbent was made using polyurethane as the precursor. The new stabilized PB showed promising adsorption efficiency. Thus, this research will open a new range of applications for all existing and emerging PB-based adsorbents., Competing Interests: Declaration of Competing Interests We have no conflicts of interest to disclose., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Gastric contractions show two specific patterns in many species, migrating motor contractions (MMC) and postprandial contractions (PPCs), that occur in the fasted and fed states, respectively. In this study, we examined the role of somatostatin (SST) in gastric motility both in vivo and in vitro using the Asian house shrew (Suncus murinus). We performed in vivo recordings of gastric motility and in vitro organ bath experiments using S. murinus, which was recently established as a small laboratory animal for use in tests of gastrointestinal motility. SST (1.65 µg kg -1  min -1 ) was intravenously administered during phase II of MMC and PPCs. Next, the effect of SST on motilin-induced gastric contractions at phase I of MMC was measured. Cyclosomatostatin (CSST), an SST receptor antagonist, was administered at the peak of phase III of MMC. In addition, the effect of SST (10 -11 -10 -9  M) on motilin-induced gastric contractions was evaluated using an organ bath experiment in vitro. In conscious, free-moving S. murinus, the administration of SST decreased the occurrence of the spontaneous phase II of MMC and PPCs. Pretreatment with SST and octreotide suppressed the induction of motilin-induced gastric contractions both in vivo and in vitro. Administration of CSST before the peak of spontaneous phase III contractions had no effect on gastric contractions. Endogenous SST is not involved in the regulation of gastric MMC and PPCs, but exogenous SST suppresses spontaneous gastric contractions. Thus, SST would be good for treating abnormal gastrointestinal motility disorders.

Motilin, a 22-amino-acid peptide produced in the upper small intestine, induces strong gastric contraction in fasted state. In many rodents, motilin and its cognate receptors exist as pseudogenes, which has delayed motilin research in the past decades. Recently, the house musk shrew (Suncus murinus) was developed as a useful model for studying motilin and gastrointestinal motility. However, due to a lack of motilin-producing cell lines and difficulties in culturing small intestinal cells, the regulatory mechanisms of motilin secretion and its messenger RNA (mRNA) transcription have remained largely unclear. In this study, we generated small intestinal organoids from S. murinus for the first time. Using methods similar to mouse organoid generation, we found crypt-like budding structures 3 days after isolating intestinal tissues. The organoids grew gradually with time. In addition, the generated organoids were able to be passaged and maintained for 6 months or longer. Motilin messenger RNA (mRNA) and immunopositive cells were observed in both S. murinus intestinal organoids and primary tissues. This is the first report of intestinal organoids in S. murinus, and our results suggest that S. murinus intestinal organoids could be useful for analyzing motilin secretion and transcription., (© 2019 International Federation for Cell Biology.)

Motilin and ghrelin were identified in the pheasant by molecular cloning, and the actions of both peptides on the contractility of gastrointestinal (GI) strips were examined in vitro. Molecular cloning indicated that the deduced amino acid sequences of the pheasant motilin and ghrelin were a 22-amino acid peptide, FVPFFTQSDIQKMQEKERIKGQ, and a 26-amino acid peptide, GSSFLSPAYKNIQQQKDTRKPTGRLH, respectively. In in vitro studies using pheasant GI strips, chicken motilin caused contraction of the proventriculus and small intestine, whereas the crop and colon were insensitive. Human motilin, but not erythromycin, caused contraction of small intestine. Chicken motilin-induced contractions in the proventriculus and ileum were not inhibited by a mammalian motilin receptor antagonist, GM109. Neither atropine (a cholinergic receptor antagonist) nor tetrodotoxin (a neuron blocker) inhibited the responses of chicken motilin in the ileum but both drugs decreased the responses to motilin in the proventriculus, suggesting that the contractile mechanisms of motilin in the proventriculus was neurogenic, different from that of the small intestine (myogenic). On the other hand, chicken and quail ghrelin did not cause contraction in any regions of pheasant GI tract. Since interaction of ghrelin and motilin has been reported in the house musk shrew, interaction of two peptides was examined. The chicken motilin-induced contractions were not modified by ghrelin, and ghrelin also did not cause any contraction under the presence of motilin, suggesting the absence of interaction in both peptides. In conclusion, both the motilin system and ghrelin system are present in the pheasant. Regulation of GI motility by motilin might be common in avian species. However, absence of ghrelin actions in any GI regions suggests the avian species-related difference in regulation of GI contractility by ghrelin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The intestinal epithelial monolayer forms a mucosal barrier between the gut microbes and the host tissue. The mucosal barrier is composed of mucins and antimicrobial peptides and proteins (AMPs). Several animal studies have reported that Paneth cells, which occupy the base of intestinal crypts, play an important role in the intestinal innate immunity by producing AMPs, such as lysozyme, Reg3 lectins, α-defensins, and group IIA secretory phospholipase A2 (GIIA sPLA2). The house musk shrew (Suncus murinus) has only a few intestinal commensal bacteria and is reported to lack Paneth cells in the intestine. Although the expression of lysozyme was reported in the suncus intestine, the expression of other AMPs has not yet been reported. Therefore, the current study was focused on GIIA sPLA2 expression in Suncus murinus. GIIA sPLA2 mRNA was found to be most abundant in the spleen and also highly expressed in the intestine. Cells expressing GIIA sPLA2 mRNA were distributed not only in the crypt, but also in the villi. In addition, intragastric injection of lipopolysaccharide increased GIIA sPLA2 expression in the small intestine of suncus. These results suggest that suncus may host unique AMP-secreting cells in the intestine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Molecular hydrogen (H 2 ) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H 2 was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H 2 in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H 2 . It suggests indirect signaling of H 2 and gastrointestinal tract is involved. Indirect effects of H 2 could be tested by giving H 2 water only before nerve injury, as preconditioning. For example, preconditioning of H 2 for certain a period (∼7 days) in Parkinson's disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H 2 in drinking water induces ghrelin production and release from the stomach via β1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood-brain barrier, activates its receptor, growth-hormone secretagogue receptor. H 2 -induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H 2 and raise intriguing preventive and therapeutic options using H 2 .

Neuromedin U (NMU) shows circadian expression in the rat pars tuberalis (PT), and is known to be suppressed by melatonin. Here we examined the involvement of adenosine in the regulation of Nmu expression. We found that the rat PT expressed adenosine receptor A2b and that an adenosine receptor agonist, NECA, stimulated Nmu expression in brain slice cultures. In vitro promoter assays revealed that NECA stimulated Nmu promoter activity via a cAMP response element (CRE) in the presence of adenosine receptor A2b. NECA also increased the levels of phosphorylated CRE-binding protein. These findings suggest that adenosine stimulates Nmu expression by activating the cAMP signaling pathway through adenosine receptor A2b in the rat PT. This is the first report to demonstrate that Nmu expression in the PT is regulated by adenosine, which acts as an intravital central metabolic signal, in addition to melatonin, which acts as an external photoperiodic environmental signal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alteration in the gastrointestinal (GI) motility and transit comprises an important component of the functional gastrointestinal disorders (FGID). Available animal GI motility and transit models are to study symptoms (delayed gastric emptying, constipation, diarrhea) rather than biological markers to develop an effective treatment that targets the underlying mechanism of altered GI motility in patients. Animal data generated from commonly used methods in human like scintigraphy, breath test and wireless motility capsule may directly translate to the clinic. However, species differences in the control mechanism or pharmacological responses of GI motility may compromise the predictive and translational value of the preclinical data to human. In this review we aim to provide a summary on animal models used to mimic GI motility alteration in FGID, and the impact of the species differences in the physiological and pharmacological responses on the translation of animal GI motility and transit data to human., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lysozyme is one of the most prominent antimicrobial peptides and has been identified from many mammalian species. However, this enzyme has not been studied in the order Insectivora, which includes the most primitive placental mammals. Here, we done the lysozyme cDNA from Suncus murinus (referred to as suncus, its laboratory name) and compare the predicted amino acid sequence to those from other mammalian species. Quantitative PCR analysis revealed a relatively higher expression of this gene in the spleen and gastrointestinal tract of suncus. The lysozyme-immunopositive (ip) cells were found mainly in the red pulp of the spleen and in the mucosa of the whole small intestine, including the follicle-associated epithelium and subepithelial dome of Peyer's patches. The lysozyme-ip cells in the small intestine were mostly distributed in the intestinal crypt, although lysozyme-expressing cells were found not only in the crypt but also in the villi. On the other hand, only a few lysozyme-ip cells were found in the villi and some granules showing intense fluorescence were located toward the lumen. As reported for other mammals, Ki67-ip cells were localized in the crypt and did not co-localize with the lysozyme-ip cells. Moreover, fasting induced a decrease in the mRNA levels of lysozyme in the intestine of suncus. In conclusion, we firstly identified the lysozyme mRNA sequence, clarified expression profile of lysozyme transcripts in suncus and found a unique distribution of lysozyme-producing cells in the suncus intestine.

Motilin (MLN), a 22-amino-acid peptide hormone, is generally present in the mucosa of the upper gastrointestinal (GI) tract, mainly the duodenum of mammals, and it regulates GI motility, especially that related to interdigestive migrating contraction. However, MLN and its receptor are absent in mice and rats, and MLN does not cause any mechanical responses in the rat and mouse GI tracts. The guinea-pig is also a rodent, but expression of the MLN gene in the guinea-pig has been reported. In the present study, two guinea-pig MLNs, FIPIFTYSELRRTQEREQNKGL found in the Ensemble Genome Database (gpMLN-1) and FVPIFTYSELRRTQEREQNKRL reported by Xu et al. (2001) (gpMLN-2), were synthesized, and their biological activities were evaluated in the rabbit duodenum and guinea-pig GI tract in vitro. Both gpMLNs showed contractile activity in longitudinal muscle strips of the rabbit duodenum. The EC 50 values of gpMLN-1 and gpMLN-2 were slightly higher than that of human MLN (hMLN), but the maximum contractions were as same as that of hMLN. Treatment with GM109 and hMLN-induced receptor desensitization decreased the contractile activity of both gpMLNs, indicating that the two gpMLN candidates are able to activate the MLN receptor (MLN-R) of the rabbit duodenum. In guinea-pig GI preparations, hMLN and gpMLNs did not show any mechanical responses in circular muscle strips from the gastric antrum or in longitudinal strips of the duodenum, ileum and colon although acetylcholine and 1,1-dimethyl-4-phenylpiperazinium (DMPP) caused definite mechanical responses. The DMPP-induced neural responses in the gastric circular muscle and ileal longitudinal muscles were not modified by gpMLN-1. Even in the gastric and ileal strips with intact mucosa, no mechanical responses were seen with either of the gpMLNs. Furthermore, RT-PCR using various primer sets failed to amplify the gpMLN-2 mRNA. In conclusion, gpMLNs including one that was already reported and the other that was newly found in a database were effective to the rabbit MLN-R, whereas they did not cause any contractions or modification of neural responses in the guinea-pig GI tract, indicating that the MLN system is vestigial and not functional in regulation of GI motility in the guinea-pig as well as in other rodents such as rats and mice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.

Several network features and information retrieval methods have been proposed to elucidate the structure of citation networks and to detect important nodes. However, it is difficult to retrieve information related to trends in an academic field and to detect cutting-edge areas from the citation network. In this paper, we propose a novel framework that detects the trend as the growth direction of a citation network using network representation learning(NRL). We presume that the linear growth of citation network in latent space obtained by NRL is the result of the iterative edge additional process of a citation network. On APS datasets and papers of some domains of the Web of Science, we confirm the existence of trends by observing that an academic field grows in a specific direction linearly in latent space. Next, we calculate each node's degree of trend-following as an indicator called the intrinsic publication year (IPY). As a result, there is a correlation between the indicator and the number of future citations. Furthermore, a word frequently used in the abstracts of cutting-edge papers (high-IPY paper) is likely to be used often in future publications. These results confirm the validity of the detected trend for predicting citation network growth., Competing Interests: The authors have declared that no competing interests exist.

Gastric contractions exhibit characteristic motor patterns in the fasted state, known as migrating motor contractions (MMC). MMC consist of three periodically repeated phases (phase I, II and III) and are known to be regulated by hormones and the autonomic and enteric nervous systems. However, the central regulation of gastric contractions in the fasted state is not completely understood. Here, we have examined the central effects of motilin, ghrelin, γ-aminobutyric acid (GABA) and L-glutamate signaling on gastric MMC by using suncus (Suncus murinus) as an animal model, because of their similar gastric motor patterns to those observed in humans and dogs. Intracerebroventricular (i.c.v.) administration of motilin and ghrelin had no effect on phase I and II contractions, respectively. Conversely, i.c.v. administration of GABA A receptor antagonist, during phase I of the MMC, evoked phase II-like contractions and significantly increased the motility index (MI). This was compared with the i.c.v. administration of GABA which inhibited spontaneous phase II contractions with a significantly decreased MI. In addition, i.c.v. administration of L-glutamate during phase I also induced phase II-like irregular contractions with a significant increase in the MI. Taken together with previous findings, these results suggest that central GABAergic and glutamatergic signaling, with the coordination of both peripheral motilin and ghrelin, regulate phase II contractions of MMC in the fasted state.

Aim: Myriad biological effects of leptin may lead to broad therapeutic applications for various metabolic diseases, including diabetes and its complications; however, in contrast to its anorexic effect, the molecular mechanisms underlying adipopenic and glucose-lowering effects of leptin have not been fully understood. Here we aim to clarify the role of hormone-sensitive lipase (HSL) in leptin's action., Methods: Wild-type (WT) and HSL-deficient (HSLKO) mice were made hyperleptinemic by two commonly-used methods: adenovirus-mediated overexpression of leptin and continuous subcutaneous infusion of leptin by osmotic pumps. The amount of food intake, body weights, organ weights, and parameters of glucose and lipid metabolism were measured., Results: Hyperleptinemia equally suppressed the food intake in WT and HSLKO mice. On the other hand, leptin-mediated fat loss and glucose-lowering were significantly blunted in the absence of HSL when leptin was overexpressed by recombinant adenovirus carrying leptin. By osmotic pumps, the fat-losing and glucose-lowering effects of leptin were milder due to lower levels of hyperleptinemia; although the difference between WT and HSLKO mice did not reach statistical significance, HSLKO mice had a tendency to retain more fat than WT mice in the face of hyperleptinemia., Conclusions: We clarify for the first time the role of HSL in leptin's effect using a genetic model: leptin-promoted fat loss and glucose-lowering are at least in part mediated via HSL-mediated lipolysis. Further studies to define the pathophysiological role of adipocyte lipases in leptin action may lead to a new therapeutic approach to circumvent leptin resistance.

This corrects the article DOI: 10.1038/srep40259.

Objectives: Milk basic protein (MBP), a mixture of proteins isolated from bovine milk, is known to increase bone formation. Ghrelin, a stomach-derived peptide hormone, also has been reported to stimulate osteoblast formation. The aim of this study was to determine whether MBP-induced bone formation is mediated via ghrelin., Methods: MBP was chronically administered to mice in their drinking water for 3 wk, and body weight, water intake, and bone mineral density were measured. Additionally, plasma bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase isoform 5b, and ghrelin concentrations were determined by enzyme-linked immunosorbent assay. To examine the direct effect of MBP on ghrelin secretion, gastric tissue culture and primary mucosal cells were stimulated by MBP., Results: The in vivo study of young, growing mice showed that chronic MBP intake for 3 wk increased the plasma ghrelin concentration and bone mineral density of the hind limb tibia. In vitro studies using minced rat gastric mucosa tissues and primary murine isolated gastric mucosal cells revealed that MBP stimulated ghrelin release in a dose-dependent manner. Moreover, MBP-induced ghrelin secretion was partly inhibited by adrenergic blockers., Conclusions: These findings suggest a novel mechanism by which MBP directly acts on ghrelin secretion. Additionally, the elevated ghrelin level induced by MBP may act as a mediator for bone formation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This work describes the whole-mount immunohistochemistry staining method in detail, using neurofilament protein antibody to label the innervation of the biliary tract in Suncus murinus (S. murinus ). First, the specimen was dissected from S. murinus and fixed in 4% paraformaldehyde (PFA). Second, an enzymatic treatment and potential endogenous peroxidase inactivation were performed. The specimen was then exposed to the primary antibody, anti-neurofilament protein antibody, for 3-6 days. It was then incubated with the secondary antibody conjugated with horseradish peroxidase. The color reaction was revealed by reacting the specimen with a 3,3'-diaminobenzidine (DAB) substrate. This method can be applied to analyze the innervation of all visceral organs. Furthermore, this protocol can also be adapted to test other neuronal antibodies, but optimization of the antibodies should be done first. This method was originally introduced by Kuratani and Tanaka 1 , 2 , 3 .

Ghrelin is abundantly produced in the stomach. Here, we found that glutamate decreased ghrelin expression and release in ghrelin-producing cells, and decreased levels of food intake and plasma acyl-ghrelin in mice. Treatment with siRNA of G protein-coupled receptor, family C, group 5, member B (GPRC5B) in ghrelin-producing cell lines completely blocked the effect of glutamate-induced ghrelin suppression. In addition, glutamate inhibited ghrelin release via the extracellular signal-regulated kinase (ERK) activity pathway, and stimulated CREB2 mRNA expression in ghrelin-producing cell lines. These results suggest that glutamate inhibits ghrelin release via ERK-CREB2 pathway. These results suggest that the GPRC5B-ERK-CREB2 pathway is involved in the inhibition of ghrelin expression and secretion in ghrelin cells., (© 2017 International Federation for Cell Biology.)

Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles., Competing Interests: We have the following interests: This work was supported in part by Nihon-Trim Co., Ltd. Shigeru Kabayama is employed by Nihon-Trim Co. Ltd. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.