bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic Insights into the Antimicrobial Actions of Metallic Nanoparticles and Their Implications for Multidrug Resistance
Authors: Shaikh Sibhghatulla , Nazam Nazia , Rizvi Syed Mohd Danish , Ahmad Khurshid , Baig Mohammad Hassan , Lee Eun Ju , Choi Inho
Published: May 2019

Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.
Tumor-Specific Reactive Oxygen Species Accelerators Improve Chimeric Antigen Receptor T Cell Therapy in B Cell Malignancies
Authors: Yoo Hyeon Joo , Liu Yibin , Wang Lei , Schubert Maria-Luisa , Hoffmann Jean-Marc , Wang Sanmei , Neuber Brigitte , Hückelhoven-Krauss Angela , Gern Ulrike , Schmitt Anita , Müller-Tidow Carsten , Dreger Peter , Mokhir Andriy , Schmitt Michael , Sellner Leopold
Published: May 2019

Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, the immunosuppressive nature of the tumor microenvironment, in particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit increased ROS levels in the tumor microenvironment with prodrugs of ROS accelerators, which are specifically activated in cancer cells. Upon activation, ROS accelerators induce further generation of ROS. This leads to an accumulation of ROS in tumor cells. We hypothesized that the latter cells will be more susceptible to CARTs. CD19-specific CARTs were generated with a CD19.CAR.CD28.CD137zeta third-generation retroviral vector. Cytotoxicity was determined by chromium-51 release assay. Influence of the ROS accelerators on viability and phenotype of CARTs was determined by flow cytometry. The combination of CARTs with the ROS accelerator PipFcB significantly increased their cytotoxicity in the Burkitt lymphoma cell lines Raji and Daudi, as well as primary chronic lymphocytic leukemia cells. Exposure of CARTs to PipFcB for 48 h did not influence T cell exhaustion, viability, or T cell subpopulations. In summary, the combination of CARTs with ROS accelerators may improve adoptive immunotherapy and help to overcome tumor microenvironment-mediated treatment resistance.
Alterations of Fatty Acid Profile May Contribute to Dyslipidemia in Chronic Kidney Disease by Influencing Hepatocyte Metabolism
Authors: Czumaj Aleksandra , Śledziński Tomasz , Carrero Juan-Jesus , Stepnowski Piotr , Sikorska-Wisniewska Malgorzata , Chmielewski Michal , Mika Adriana
Published: May 2019

Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis (fatty acid synthase (FASN) increased 13.7 ± 3.5 times, stearoyl-CoA desaturase 1 (SCD1) increased 4.26 ± 0.36 times), and very low density lipoprotein (VLDL) formation (apolipoprotein B (ApoB) increased 7.35 ± 1.5 times, microsomal triacylglycerol transfer protein (MTTP) increased 2.74 ± 0.43 times). In conclusion, there were progressive alterations in serum FA composition of patients with CKD. These alterations may partly contribute to CKD hypertriglyceridemia by influencing hepatocyte expression of genes of lipid synthesis and release.
HMGA2 Contributes to Distant Metastasis and Poor Prognosis by Promoting Angiogenesis in Oral Squamous Cell Carcinoma
Authors: Sakata Junki , Hirosue Akiyuki , Yoshida Ryoji , Kawahara Kenta , Matsuoka Yuichiro , Yamamoto Tatsuro , Nakamoto Masafumi , Hirayama Masatoshi , Takahashi Nozomu , Nakamura Takuya , Arita Hidetaka , Nakashima Hikaru , Nagata Masashi , Hiraki Akimitsu , Shinohara Masanori , Nakayama Hideki
Published: May 2019

The highly malignant phenotype of oral squamous cell carcinoma (OSCC), including the presence of nodal and distant metastasis, reduces patient survival. High-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor that is involved in advanced malignant phenotypes and poor prognosis in several human cancers. However, its biological role in OSCC remains to be elucidated. The purpose of this study was to determine the clinical significance and role of HMGA2 in the malignant potential of OSCC. We first investigated the expression pattern of HMGA2 and its clinical relevance in 110 OSCC specimens using immunohistochemical staining. In addition, we examined the effects HMGA2 on the regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, which are related to angiogenesis, in vitro. High expression of HMGA2 was significantly correlated with distant metastasis and poor prognosis. Further, HMGA2 depletion in OSCC cells reduced the expression of angiogenesis genes. In OSCC tissues with high HMGA2 expression, angiogenesis genes were increased and a high proportion of blood vessels was observed. These findings suggest that HMGA2 plays a significant role in the regulation of angiogenesis and might be a potential biomarker to predict distant metastasis and prognosis in OSCC.
Role of Macrophages in Cardioprotection
Authors: Yap Jonathan , Cabrera-Fuentes Hector A. , Irei Jason , Hausenloy Derek J. , Boisvert William A.
Published: May 2019

Cardiovascular diseases are the leading cause of mortality worldwide. It is widely known that non-resolving inflammation results in atherosclerotic conditions, which are responsible for a host of downstream pathologies including thrombosis, myocardial infarction (MI), and neurovascular events. Macrophages, as part of the innate immune response, are among the most important cell types in every stage of atherosclerosis. In this review we discuss the principles governing macrophage function in the healthy and infarcted heart. More specifically, how cardiac macrophages participate in myocardial infarction as well as cardiac repair and remodeling. The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction. In the early “inflammatory” stage of MI, resident cardiac macrophages are replaced by classically activated macrophages derived from the bone marrow and spleen. And while the macrophage population shifts towards an alternatively activated phenotype, the inflammatory response subsides giving way to the “reparative/proliferative” phase. Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection. Promising results demonstrate innovative concepts; one employing a subset of yolk sac-derived, cardiac macrophages that have complete restorative capacity in the injured myocardium of neonatal mice, and in another example, post-conditioning of cardiac macrophages with cardiosphere-derived cells significantly improved patient’s post-MI diagnoses.
Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy
Authors: Kim Young Eun , Sung Se In , Chang Yun Sil , Ahn So Yoon , Sung Dong Kyung , Park Won Soon
Published: May 2019

We investigated whether thrombin preconditioning of human Wharton’s jelly–derived mesenchymal stem cells (MSCs) improves paracrine potency and thus the therapeutic efficacy of naïve MSCs against severe hypoxic ischemic encephalopathy (HIE). Thrombin preconditioning significantly enhances the neuroprotective anti-oxidative, anti-apoptotic, and anti-cytotoxic effects of naïve MSCs against oxygen–glucose deprivation (OGD) of cortical neurons in vitro. Severe HIE was induced in vivo using unilateral carotid artery ligation and hypoxia for 2 h and confirmed using brain magnetic resonance imaging (MRI) involving >40% of ipsilateral hemisphere at postnatal day (P) 7 in newborn rats. Delayed intraventricular transplantation of 1 × 105 thrombin preconditioned but not naïve MSCs at 24 h after hypothermia significantly enhanced observed anti-inflammatory, anti-astroglial, and anti-apoptotic effects and the ensuing brain infarction; behavioral tests, such as cylinder rearing and negative geotaxis tests, were conducted at P42. In summary, thrombin preconditioning of human Wharton’s jelly-derived MSCs significantly boosted the neuroprotective effects of naïve MSCs against OGD in vitro by enhancing their anti-oxidative, anti-apoptotic, and anti-cytotoxic effects, and significantly attenuated the severe HIE-induced brain infarction and improved behavioral function tests in vivo by maximizing their paracrine anti-inflammatory, anti-astroglial, and anti-apoptotic effects.
SpPKE1, a Multiple Stress-Responsive Gene Confers Salt Tolerance in Tomato and Tobacco
Authors: Li Jinhua , Chen Chunrui , Wei Juanjuan , Pan Yu , Su Chenggang , Zhang Xingguo
Published: May 2019

Understanding the mechanism of abiotic-tolerance and producing germplasm of abiotic tolerance are important in plant research. Wild species often show more tolerance of environmental stress factors than their cultivated counterparts. Genes from wild species show potential abilities to improve abiotic resistance in cultivated species. Here, a tomato proline-, lysine-, and glutamic-rich type gene SpPKE1 was isolated from abiotic-resistant species (Solanum pennellii LA0716) for over-expression in tomato and tobacco for salt tolerance. The protein encoded by SpPKE1 was predominantly localized in the cytoplasm in tobacco. SpPKE1 and SlPKE1 (from cultivated species S. lycopersicum cv. M82) shared 89.7% similarity in amino acid sequences and their transcripts abundance in flowers and fruits was reduced by the imposition of drought or oxidative stress and the exogenous supply of abscisic acid. The DNA of the PKE1 promoter was highly methylated in fruit and leaf, and the methylation of the coding sequence in leaf was significantly higher than that in fruit at different development stages. The over-expression of SpPKE1 under the control of a CaMV (Cauliflower Mosaic Virus) 35S promoter in transgenic tomato and tobacco plants enhanced their tolerance to salt stress. PKE1 was downregulated by abiotic stresses but enhanced the plant’s salt stress tolerance. Therefore, this gene may be involved in post-transcriptional regulation and may be an important candidate for molecular breeding of salt-tolerant plants.
Jasmonic Acid Signaling Pathway in Plants
Authors: Ruan Jingjun , Zhou Yuexia , Zhou Meiliang , Yan Jun , Khurshid Muhammad , Weng Wenfeng , Cheng Jianping , Zhang Kaixuan
Published: May 2019

Jasmonic acid (JA) and its precursors and dervatives, referred as jasmonates (JAs) are important molecules in the regulation of many physiological processes in plant growth and development, and especially the mediation of plant responses to biotic and abiotic stresses. JAs biosynthesis, perception, transport, signal transduction and action have been extensively investigated. In this review, we will discuss the initiation of JA signaling with a focus on environmental signal perception and transduction, JA biosynthesis and metabolism, transport of signaling molecules (local transmission, vascular bundle transmission, and airborne transportation), and biological function (JA signal receptors, regulated transcription factors, and biological processes involved).
Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model
Authors: Buckinx An , Van Den Herrewegen Yana , Pierre Anouk , Cottone Eleonora , Ben Haj Salah Khoubaib , Fehrentz Jean-Alain , Kooijman Ron , De Bundel Dimitri , Smolders Ilse
Published: May 2019

The ghrelin system has received substantial recognition as a potential target for novel anti-seizure drugs. Ghrelin receptor (ghrelin-R) signaling is complex, involving Gαq/11, Gαi/o, Gα12/13, and β-arrestin pathways. In this study, we aimed to deepen our understanding regarding signaling pathways downstream the ghrelin-R responsible for mediating anticonvulsive effects in a kindling model. Mice were administered the proconvulsive dopamine 1 receptor-agonist, SKF81297, to gradually induce a kindled state. Prior to every SKF81297 injection, mice were treated with a ghrelin-R full agonist (JMV-1843), a Gαq and Gα12 biased ligand unable to recruit β-arrestin (YIL781), a ghrelin-R antagonist (JMV-2959), or saline. Mice treated with JMV-1843 had fewer and less severe seizures compared to saline-treated controls, while mice treated with YIL781 experienced longer and more severe seizures. JMV-2959 treatment did not lead to differences in seizure severity and number. Altogether, these results indicate that the Gαq or Gα12 signaling pathways are not responsible for mediating JMV-1843′s anticonvulsive effects and suggest a possible involvement of β-arrestin signaling in the anticonvulsive effects mediated by ghrelin-R modulation.
Phloretin Suppresses Bone Morphogenetic Protein-2-Induced Osteoblastogenesis and Mineralization via Inhibition of Phosphatidylinositol 3-kinases/Akt Pathway
Authors: Takeno Ayumu , Kanazawa Ippei , Tanaka Ken-ichiro , Notsu Masakazu , Sugimoto Toshitsugu
Published: May 2019

Phloretin has pleiotropic effects, including glucose transporter (GLUT) inhibition. We previously showed that phloretin promoted adipogenesis of bone marrow stromal cell (BMSC) line ST2 independently of GLUT1 inhibition. This study investigated the effect of phloretin on osteoblastogenesis of ST2 cells and osteoblastic MC3T3-E1 cells. Treatment with 10 to 100 µM phloretin suppressed mineralization and expression of osteoblast differentiation markers, such as alkaline phosphatase (ALP), osteocalcin (OCN), type 1 collagen, runt-related transcription factor 2 (Runx2), and osterix (Osx), while increased adipogenic markers, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid-binding protein 4, and adiponectin. Phloretin also inhibited mineralization and decreased osteoblast differentiation markers of MC3T3-E1 cells. Phloretin suppressed phosphorylation of Akt in ST2 cells. In addition, treatment with a phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor, LY294002, suppressed the mineralization and the expression of osteoblast differentiation markers other than ALP. GLUT1 silencing by siRNA did not affect mineralization, although it decreased the expression of OCN and increased the expression of ALP, Runx2, and Osx. The effects of GLUT1 silencing on osteoblast differentiation markers and mineralization were inconsistent with those of phloretin. Taken together, these findings suggest that phloretin suppressed osteoblastogenesis of ST2 and MC3T3-E1 cells by inhibiting the PI3K/Akt pathway, suggesting that the effects of phloretin may not be associated with glucose uptake inhibition.
Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors
Authors: Kucheryavykh Lilia Y. , Ortiz-Rivera Jescelica , Kucheryavykh Yuriy V. , Zayas-Santiago Astrid , Diaz-Garcia Amanda , Inyushin Mikhail Y.
Published: May 2019

Immunostaining with specific antibodies has shown that innate amyloid beta (Aβ) is accumulated naturally in glioma tumors and nearby blood vessels in a mouse model of glioma. In immunofluorescence images, Aβ peptide coincides with glioma cells, and enzyme-linked immunosorbent assay (ELISA) have shown that Aβ peptide is enriched in the membrane protein fraction of tumor cells. ELISAs have also confirmed that the Aβ(1–40) peptide is enriched in glioma tumor areas relative to healthy brain areas. Thioflavin staining revealed that at least some amyloid is present in glioma tumors in aggregated forms. We may suggest that the presence of aggregated amyloid in glioma tumors together with the presence of Aβ immunofluorescence coinciding with glioma cells and the nearby vasculature imply that the source of Aβ peptides in glioma can be systemic Aβ from blood vessels, but this question remains unresolved and needs additional studies.
The Dark Matter of Large Cereal Genomes: Long Tandem Repeats
Authors: Kapustová Veronika , Tulpová Zuzana , Toegelová Helena , Novák Petr , Macas Jiří , Karafiátová Miroslava , Hřibová Eva , Doležel Jaroslav , Šimková Hana
Published: May 2019

Reference genomes of important cereals, including barley, emmer wheat and bread wheat, were released recently. Their comparison with genome size estimates obtained by flow cytometry indicated that the assemblies represent not more than 88–98% of the complete genome. This work is aimed at identifying the missing parts in two cereal genomes and proposing techniques to make the assemblies more complete. We focused on tandemly organised repetitive sequences, known to be underrepresented in genome assemblies generated from short-read sequence data. Our study found arrays of three tandem repeats with unit sizes of 1242 to 2726 bp present in the bread wheat reference genome generated from short reads. However, this and another wheat genome assembly employing long PacBio reads failed in integrating correctly the 2726-bp repeat in the pseudomolecule context. This suggests that tandem repeats of this size, frequently incorporated in unassigned scaffolds, may contribute to shrinking of pseudomolecules without reducing size of the entire assembly. We demonstrate how this missing information may be added to the pseudomolecules with the aid of nanopore sequencing of individual BAC clones and optical mapping. Using the latter technique, we identified and localised a 470-kb long array of 45S ribosomal DNA absent from the reference genome of barley.
Physiological and Proteomic Responses of Mulberry Trees (Morus alba. L.) to Combined Salt and Drought Stress
Authors: Liu Yan , Ji Dongfeng , Turgeon Robert , Chen Jine , Lin Tianbao , Huang Jing , Luo Jie , Zhu Yan , Zhang Cankui , Lv Zhiqiang
Published: May 2019

Intensive investigations have been conducted on the effect of sole drought or salinity stress on the growth of plants. However, there is relatively little knowledge on how plants, particularly woody species, respond to a combination of these two stresses although these stresses can simultaneously occur in the field. In this study, mulberry, an economically important resource for traditional medicine, and the sole food of domesticated silkworms was subjected to a combination of salt and drought stress and analyzed by physiological methods and TMT-based proteomics. Stressed mulberry exhibited significant alteration in physiological parameters, including root/shoot ratio, chlorophyll fluorescence, total carbon, and ion reallocation. A total of 577 and 270 differentially expressed proteins (DEPs) were identified from the stressed leaves and roots, respectively. Through KEGG analysis, these DEPs were assigned to multiple pathways, including carbon metabolism, photosynthesis, redox, secondary metabolism, and hormone metabolism. Among these pathways, the sucrose related metabolic pathway was distinctly enriched in both stressed leaves and roots, indicating an important contribution in mulberry under stress condition. The results provide a comprehensive understanding of the adaptive mechanism of mulberry in response to salt and drought stress, which will facilitate further studies on innovations in terms of crop performance.
Roles of Natural Killer T Cells and Natural Killer Cells in Kidney Injury
Authors: Uchida Takahiro , Ito Seigo , Kumagai Hiroo , Oda Takashi , Nakashima Hiroyuki , Seki Shuhji
Published: May 2019

Mouse natural killer T (NKT) cells and natural killer (NK) cells are innate immune cells that are highly abundant in the liver. In addition to their already-known antitumor and antimicrobial functions, their pathophysiological roles in the kidney have recently become evident. Under normal circumstances, the proportion of activated NKT cells in the kidney increases with age. Administration of a synthetic sphingoglycolipid ligand (alpha-galactosylceramide) further activates NKT cells, resulting in injury to renal vascular endothelial cells via the perforin-mediated pathway and tubular epithelial cells via the TNF-α/Fas ligand pathway, causing acute kidney injury (AKI) with hematuria. Activation of NKT cells by common bacterial DNA (CpG-ODN) also causes AKI. In addition, NKT cells together with B cells play significant roles in experimental lupus nephritis in NZB/NZW F1 mice through their Th2 immune responses. Mouse NK cells are also assumed to be involved in various renal diseases, and there may be complementary roles shared between NKT and NK cells. Human CD56+ T cells, a functional counterpart of mouse NKT cells, also damage renal cells through a mechanism similar to that of mice. A subpopulation of human CD56+ NK cells also exert strong cytotoxicity against renal cells and contribute to the progression of renal fibrosis.
Nociceptor Signalling through ion Channel Regulation via GPCRs
Authors: Salzer Isabella , Ray Sutirtha , Schicker Klaus , Boehm Stefan
Published: May 2019

The prime task of nociceptors is the transformation of noxious stimuli into action potentials that are propagated along the neurites of nociceptive neurons from the periphery to the spinal cord. This function of nociceptors relies on the coordinated operation of a variety of ion channels. In this review, we summarize how members of nine different families of ion channels expressed in sensory neurons contribute to nociception. Furthermore, data on 35 different types of G protein coupled receptors are presented, activation of which controls the gating of the aforementioned ion channels. These receptors are not only targeted by more than 20 separate endogenous modulators, but can also be affected by pharmacotherapeutic agents. Thereby, this review provides information on how ion channel modulation via G protein coupled receptors in nociceptors can be exploited to provide improved analgesic therapy.
Virtual Screening Guided Design, Synthesis and Bioactivity Study of Benzisoselenazolones (BISAs) on Inhibition of c-Met and Its Downstream Signalling Pathways
Authors: Zhang Siqi , Song Qiaoling , Wang Xueting , Wei Zhiqiang , Yu Rilei , Wang Xin , Jiang Tao
Published: May 2019

c-Met is a transmembrane receptor tyrosine kinase and an important therapeutic target for anticancer drugs. In this study, we designed a small library containing 300 BISAs molecules that consisted of carbohydrates, amino acids, isothiourea, tetramethylthiourea, guanidine and heterocyclic groups and screened c-Met targeting compounds using docking and MM/GBSA. Guided by virtual screening, we synthesised a series of novel compounds and their activity on inhibition of the autophosphorylation of c-Met and its downstream signalling pathway proteins were evaluated. We found a panel of benzisoselenazolones (BISAs) obtained by introducing isothiourea, tetramethylthiourea and heterocyclic groups into the C-ring of Ebselen, including 7a, 7b, 8a, 8b and 12c (with IC50 values of less than 20 μM in MET gene amplified lung cancer cell line EBC-1), exhibited more potent antitumour activity than Ebselen by cell growth assay combined with in vitro biochemical assays. In addition, we also tested the antitumour activity of three cancer cell lines without MET gene amplification/activation, including DLD1, MDA-MB-231 and A549. The neuroblastoma SK-N-SH cells with HGF overexpression which activates MET signalling are sensitive to MET inhibitors. The results reveal that our compounds may be nonspecific multitarget kinase inhibitors, just like type-II small molecule inhibitors. Western blot analysis showed that these inhibitors inhibited autophosphorylation of c-MET, and its downstream signalling pathways, such as PI3K/AKT and MARK/ERK. Results suggest that bensoisoselenones can be used as a scaffold for the design of c-Met inhibiting drug leads, and this study opens up new possibilities for future antitumour drug design.
Topical Spilanthol Inhibits MAPK Signaling and Ameliorates Allergic Inflammation in DNCB-Induced Atopic Dermatitis in Mice
Authors: Huang Wen-Chung , Huang Chun-Hsun , Hu Sindy , Peng Hui-Ling , Wu Shu-Ju
Published: May 2019

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.
Deep Insight into the Transcriptome of the Single Silk Gland of Bombyx mori
Authors: Shi Run , Ma Sanyuan , He Ting , Peng Jian , Zhang Tong , Chen Xiaoxu , Wang Xiaogang , Chang Jiasong , Xia Qingyou , Zhao Ping
Published: May 2019

The silk gland synthesizes and secretes a large amount of protein and stores liquid silk protein at an extremely high concentration. Interestingly, silk proteins and serine protease inhibitors are orderly arranged in the silk gland lumen and cocoon shells. Silk fiber formation and the spinning mechanism have not been fully elucidated. Therefore, we conducted a comparative transcriptome analysis of seven segments of the single silk gland to characterize internal changes in the silk gland during the 5th instar of mature larvae. In total, 3121 differentially expressed genes were identified in the seven segments. Genes highly expressed in the middle silk gland (MSG) were mainly involved in unsaturated fatty acid biosynthesis, fatty acid metabolism, apoptosis—fly, and lysosome pathways, whereas genes highly expressed in the posterior silk gland (PSG) were mainly involved in ribosome, proteasome, citrate cycle, and glycolysis/gluconeogenesis pathways. Thus, the MSG and PSG differ greatly in energy source use and function. Further, 773 gradually upregulated genes (from PSG to MSG) were involved in energy metabolism, silk protein synthesis, and secretion, suggesting that these genes play an important role in silk fiber formation. Our findings provide insights into the mechanism of silk protein synthesis and transport and silk fiber formation.
Effect of PHRs and PCPs on Microalgal Growth, Metabolism and Microalgae-Based Bioremediation Processes: A Review
Authors: Miazek Krystian , Brozek-Pluska Beata
Published: May 2019

In this review, the effect of pharmaceuticals (PHRs) and personal care products (PCPs) on microalgal growth and metabolism is reported. Concentrations of various PHRs and PCPs that cause inhibition and toxicity to growths of different microalgal strains are summarized and compared. The effect of PHRs and PCPs on microalgal metabolism (oxidative stress, enzyme activity, pigments, proteins, lipids, carbohydrates, toxins), as well as on the cellular morphology, is discussed. Literature data concerning the removal of PHRs and PCPs from wastewaters by living microalgal cultures, with the emphasis on microalgal growth, are gathered and discussed. The potential of simultaneously bioremediating PHRs/PCPs-containing wastewaters and cultivating microalgae for biomass production in a single process is considered. In the light of reviewed data, the feasibility of post-bioremediation microalgal biomass is discussed in terms of its contamination, biosafety and further usage for production of value-added biomolecules (pigments, lipids, proteins) and biomass as a whole.
Slc7a11 Modulated by POU2F1 is Involved in Pigmentation in Rabbit
Authors: Chen Yang , Hu Shuaishuai , Mu Lin , Zhao Bohao , Wang Manman , Yang Naisu , Bao Guolian , Zhu Cigen , Wu Xinsheng
Published: May 2019

Solute carrier family 7 member 11 (Slc7a11) is a cystine/glutamate xCT transporter that controls the production of pheomelanin pigment to change fur and skin color in animals. Previous studies have found that skin expression levels of Slc7a11 varied significantly with fur color in Rex rabbits. However, the molecular regulation mechanism of Slc7a11 in pigmentation is unknown. Here, rabbit melanocytes were first isolated and identified. The distribution and expression pattern of Slc7a11 was confirmed in skin from rabbits with different fur colors. Slc7a11 affected the expression of pigmentation related genes and thus affected melanogenesis. Meanwhile, Slc7a11 decreased melanocyte apoptosis, but inhibition of Slc7a11 enhanced apoptosis. Furthermore, the POU2F1 protein was found to bind to the −713 to −703 bp region of Slc7a11 promoter to inhibit its activity in a dual-luciferase reporter and site-directed mutagenesis assay. This study reveals the function of the Slc7a11 in melanogenesis and provides in-depth analysis of the mechanism of fur pigmentation.
Development of a Virtual Reality-Based Game Approach for Supporting Sensory Processing Disorders Treatment
Authors: Rossi Henrique , Prates Raquel , Santos Sibele , Ferreira Renato
Published: May 2019

Serious games for health are those that are not aimed solely at entertainment, but rather at supporting health treatments. In this paper, we develop and assess the proposal of a Virtual Reality (VR) game aimed at supporting Sensory Processing Disorder (SPD) treatment. SPD is a condition which affects the integration and processing of the various stimuli coming from inside and outside of the body and its treatment involves providing patients with controlled sensory stimuli. Our goal is to investigate whether a Virtual Reality game that can stimulate different sensory systems could be useful in SPD treatment. In order to do so, we have designed and developed Imaginator, a VR Roller Coaster Game connected with a Head Mounted-Display (HMD) which can be customized by therapists to adjust its stimuli to different patients’ needs in therapy. Imaginator was assessed by five occupational therapists through its use in their treatment sessions. Each therapist had the game available in their therapy environment for around 2–3 weeks. They were instructed to use the game whenever they thought it could be interesting to a patient’s treatment. After the trial period, they were interviewed about their experience in using the game and their perception of its impact in therapy sessions. Our results show that therapists in general perceived Imaginator as having a positive effects in patients’ treatment. They noticed that it was able to stimulate different senses, and they reported that in some cases it was able to help patients relax, increase their concentration and even work as an encouragement to explore similar activities in the physical world. There were a few patients who experienced some adverse reactions, such as nausea, but nothing that they felt was worrying or that could prevent the game from being used.
Open Source Completely 3-D Printable Centrifuge
Authors: Sule Salil S. , Petsiuk Aliaksei L. , Pearce Joshua M.
Published: May 2019

Centrifuges are commonly required devices in medical diagnostics facilities as well as scientific laboratories. Although there are commercial and open source centrifuges, the costs of the former and the required electricity to operate the latter limit accessibility in resource-constrained settings. There is a need for low-cost, human-powered, verified, and reliable lab-scale centrifuges. This study provides the designs for a low-cost 100% 3-D printed centrifuge, which can be fabricated on any low-cost RepRap-class (self-replicating rapid prototyper) fused filament fabrication (FFF)- or fused particle fabrication (FPF)-based 3-D printer. In addition, validation procedures are provided using a web camera and free and open source software. This paper provides the complete open source plans, including instructions for the fabrication and operation of a hand-powered centrifuge. This study successfully tested and validated the instrument, which can be operated anywhere in the world with no electricity inputs, obtaining a radial velocity of over 1750 rpm and over 50 N of relative centrifugal force. Using commercial filament, the instrument costs about U.S. $25, which is less than half of all commercially available systems. However, the costs can be dropped further using recycled plastics on open source systems for over 99% savings. The results are discussed in the context of resource-constrained medical and scientific facilities.
Conical Nanoindentation Allows Azimuthally Independent Hardness Determination in Geological and Biogenic Minerals
Authors: Böhm Corinna F. , Feldner Patrick , Merle Benoit , Wolf Stephan E.
Published: May 2019

The remarkable mechanical performance of biominerals often relies on distinct crystallographic textures, which complicate the determination of the nanohardness from indentations with the standard non-rotational-symmetrical Berkovich punch. Due to the anisotropy of the biomineral to be probed, an azimuthal dependence of the hardness arises. This typically increases the standard deviation of the reported hardness values of biominerals and impedes comparison of hardness values across the literature and, as a result, across species. In this paper, we demonstrate that an azimuthally independent nanohardness determination can be achieved by using a conical indenter. It is also found that conical and Berkovich indentations yield slightly different hardness values because they result in different pile-up behaviors and because of technical limitations on the fabrication of perfectly equivalent geometries. For biogenic crystals, this deviation of hardness values between indenters is much lower than the azimuthal variation in non-rotational-symmetrical Berkovich indentations.
pH-Sensitive Ratiometric Fluorescent Probe for Evaluation of Tumor Treatments
Authors: Zhang Peisen , Meng Junli , Li Yingying , Wang Zihua , Hou Yi
Published: May 2019

Determining therapeutic efficacy is critical for tumor precision theranostics. In order to monitor the efficacy of anti-cancer drugs (e.g., Paclitaxel), a pH-sensitive ratiometric fluorescent imaging probe was constructed. The pH-sensitive ratiometric fluorescent dye ANNA was covalently coupled to the N-terminal of the cell-penetrating TAT peptide through an amidation reaction (TAT-ANNA). The in vitro cellular experiments determined that the TAT-ANNA probe could penetrate the cell membrane and image the intracellular pH in real time. The in vivo experiments were then carried out, and the ratiometric pH response to the state of the tumor was recorded immediately after medication. The TAT-ANNA probe was successfully used to monitor the pharmacodynamics of anti-cancer drugs in vivo.
Corrosion Evaluation of 316L Stainless Steel in CNT-Water Nanofluid: Effect of CNTs Loading
Authors: Abdeen Dana H. , Atieh Muataz A. , Merzougui Belabbes , Khalfaoui Walid
Published: May 2019

Polarization resistance and potentiodynamic scan testing were performed on 316L stainless steel (SS) at room temperature in carbon nanotube (CNT)-water nanofluid. Different CNT loadings of 0.05, 0.1, 0.3 and 0.5 wt% were suspended in deionized water using gum arabic (GA) surfactant. Corrosion potential, Tafel constants, corrosion rates and pitting potential values indicated better corrosion performance in the presence of CNTs with respect to samples tested in GA-water solutions. According to Gibbs free energy of adsorption, CNTs were physically adsorbed into the surface of the metal, and this adsorption followed Langmuir adsorption isotherm type II. Samples tested in CNT nanofluid revealed a corrosion performance comparable to that of tap water and better than that for GA-water solutions. Among all samples tested in CNT nanofluids, the lowest corrosion rate was attained with 0.1 wt% CNT nanofluid, while the highest value was obtained with 0.5 wt% CNT nanofluid. At higher CNT concentrations, accumulated CNTs might form active anodic sites and increase the corrosion rate. SEM images for samples of higher CNT loadings were observed to have higher pit densities and diameters.
Analysis on the Effects of the Human Body on the Performance of Electro-Textile Antennas for Wearable Monitoring and Tracking Application
Authors: Abd Rahman Nurul Huda , Yamada Yoshihide , Amin Nordin Muhammad Shakir
Published: May 2019

Previous works have shown that wearable antennas can operate ideally in free space; however, degradation in performance, specifically in terms of frequency shifts and efficiency was observed when an antenna structure was in close proximity to the human body. These issues have been highlighted many times yet, systematic and numerical analysis on how the dielectric characteristics may affect the technical behavior of the antenna has not been discussed in detail. In this paper, a wearable antenna, developed from a new electro-textile material has been designed, and the step-by-step manufacturing process is presented. Through analysis of the frequency detuning effect, the on-body behavior of the antenna is evaluated by focusing on quantifying the changes of its input impedance and near-field distribution caused by the presence of lossy dielectric material. When the antenna is attached to the top of the body fat phantom, there is an increase of 17% in impedance, followed by 19% for the muscle phantom and 20% for the blood phantom. These phenomena correlate with the electric field intensities (V/m) observed closely at the antenna through various layers of mediums (z-axis) and along antenna edges (y-axis), which have shown significant increments of 29.7% in fat, 35.3% in muscle and 36.1% in blood as compared to free space. This scenario has consequently shown that a significant amount of energy is absorbed in the phantoms instead of radiated to the air which has caused a substantial drop in efficiency and gain. Performance verification is also demonstrated by using a fabricated human muscle phantom, with a dielectric constant of 48, loss tangent of 0.29 and conductivity of 1.22 S/m.
Improving the Thermoelectric Properties of the Half-Heusler Compound VCoSb by Vanadium Vacancy
Authors: Huang Lihong , Wang Junchen , Mo Xiaobo , Lei Xiaobo , Ma Sude , Wang Chao , Zhang Qinyong
Published: May 2019

The effects of V vacancy on the thermoelectric performance of the half-Heusler compound VCoSb have been investigated in this study. A certain amount of CoSb secondary phase is generated in the VCoSb matrix when the content of V vacancy is more than 0.1 at%. According to the results, a ZT value of 0.6, together with a power factor of 29 μW cm−1 K−2 at 873 K, were achieved for the nonstoichiometric sample V0.9CoSb. This proved that moderate V vacancy could improve the thermoelectric (TE) properties of VCoSb. The noticeable improvements are mainly owing to the incremental Seebeck coefficient, which may benefit from the optimized carrier concentration. However, too much V vacancy will result in more CoSb impurity and deteriorate the TE performances of VCoSb owing to the increased thermal conductivity.
Microstructure and Impact Toughness of Local-Dry Keyhole Tungsten Inert Gas Welded Joints
Authors: Cui Shuwan , Xian Zhiyong , Shi Yonghua , Liao Baoyi , Zhu Tao
Published: May 2019

In this paper, the microstructure and impact toughness of a S32101 duplex stainless steel underwater local-dry keyhole tungsten inert gas welded joint were studied. The impact toughness value of the underwater weld metal reached 78% of the onshore weld metal, which is in accordance with the underwater welding standards. The proportion of austenite in the underwater weld metal was 0.9% lower than that of the onshore weld metal. The proportion of the Σ3 coincidence site lattice boundaries and random phase boundaries in the underwater weld metal, which significantly influence the impact toughness of the weld metal, were smaller than that of the onshore weld metal.
Investigation on Effect of Strain Rate and Heat Generation on Traverse Force in FSW of Dissimilar Aerospace Grade Aluminium Alloys
Authors: Khan Noor Zaman , Bajaj Dhruv , Siddiquee Arshad Noor , Khan Zahid A. , Abidi Mustufa Haider , Umer Usama , Alkhalefah Hisham
Published: May 2019

The emergence of the aerospace sector requires efficient joining of aerospace grade aluminium alloys. For large-scale industrial practices, achievement of optimum friction stir welding (FSW) parameters is chiefly aimed at obtaining maximum strain rate in deforming material with least application of traverse force on the tool pin. Exact computation of strain rate is not possible due to complex and unexposed material flow kinematics. Estimation using micro-structural evolution serves as one of the very few methods applicable to analyze the yet unmapped interdependence of strain rate and traverse force. Therefore, the present work assessed strain rate in the stir zone using Zener Holloman parameter. The maximum and minimum strain rates of 6.95 and 0.31 s−1 were obtained for highest and least traverse force, respectively.
Mechanical Properties and Applications of Recycled Polycarbonate Particle Material Extrusion-Based Additive Manufacturing
Authors: Reich Matthew J. , Woern Aubrey L. , Tanikella Nagendra G. , Pearce Joshua M.
Published: May 2019

Past work has shown that particle material extrusion (fused particle fabrication (FPF)/fused granular fabrication (FGF)) has the potential for increasing the use of recycled polymers in 3D printing. This study extends this potential to high-performance (high-mechanical-strength and heat-resistant) polymers using polycarbonate (PC). Recycled PC regrind of approximately 25 mm2 was 3D printed with an open-source Gigabot X and analyzed. A temperature and nozzle velocity matrix was used to find useful printing parameters, and a print test was used to maximize the output for a two-temperature stage extruder for PC. ASTM type 4 tensile test geometries as well as ASTM-approved compression tests were used to determine the mechanical properties of PC and were compared with filament printing and the bulk virgin material. The results showed the tensile strength of parts manufactured from the recycled PC particles (64.9 MPa) were comparable to that of the commercial filament printed on desktop (62.2 MPa) and large-format (66.3 MPa) 3D printers. Three case study applications were investigated: (i) using PC as a rapid molding technology for lower melting point thermoplastics, (ii) printed parts for high temperature applications, and (iii) printed parts for high-strength applications. The results show that recycled PC particle-based 3D printing can produce high-strength and heat-resistant products at low costs.
CO-Releasing Materials: An Emphasis on Therapeutic Implications, as Release and Subsequent Cytotoxicity Are the Part of Therapy
Authors: Faizan Muhammad , Muhammad Niaz , Niazi Kifayat Ullah Khan , Hu Yongxia , Wang Yanyan , Wu Ya , Sun Huaming , Liu Ruixia , Dong Wensheng , Zhang Weiqiang , Gao Ziwei
Published: May 2019

The CO-releasing materials (CORMats) are used as substances for producing CO molecules for therapeutic purposes. Carbon monoxide (CO) imparts toxic effects to biological organisms at higher concentration. If this characteristic is utilized in a controlled manner, it can act as a cell-signaling agent for important pathological and pharmacokinetic functions; hence offering many new applications and treatments. Recently, research on therapeutic applications using the CO treatment has gained much attention due to its nontoxic nature, and its injection into the human body using several conjugate systems. Mainly, there are two types of CO insertion techniques into the human body, i.e., direct and indirect CO insertion. Indirect CO insertion offers an advantage of avoiding toxicity as compared to direct CO insertion. For the indirect CO inhalation method, developers are facing certain problems, such as its inability to achieve the specific cellular targets and how to control the dosage of CO. To address these issues, researchers have adopted alternative strategies regarded as CO-releasing molecules (CORMs). CO is covalently attached with metal carbonyl complexes (MCCs), which generate various CORMs such as CORM-1, CORM-2, CORM-3, ALF492, CORM-A1 and ALF186. When these molecules are inserted into the human body, CO is released from these compounds at a controlled rate under certain conditions or/and triggers. Such reactions are helpful in achieving cellular level targets with a controlled release of the CO amount. However on the other hand, CORMs also produce a metal residue (termed as i-CORMs) upon degradation that can initiate harmful toxic activity inside the body. To improve the performance of the CO precursor with the restricted development of i-CORMs, several new CORMats have been developed such as micellization, peptide, vitamins, MOFs, polymerization, nanoparticles, protein, metallodendrimer, nanosheet and nanodiamond, etc. In this review article, we shall describe modern ways of CO administration; focusing primarily on exclusive features of CORM’s tissue accumulations and their toxicities. This report also elaborates on the kinetic profile of the CO gas. The comprehension of developmental phases of CORMats shall be useful for exploring the ideal CO therapeutic drugs in the future of medical sciences.