bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum secret sharing with identity authentication based on Bell states
Authors: Abulkasim Hussein , Hamad Safwat , Khalifa Amal , El Bahnasy Khalid
Published: May 2017

Quantum secret sharing techniques allow two parties or more to securely share a key, while the same number of parties or less can efficiently deduce the secret key. In this paper, we propose an authenticated quantum secret sharing protocol, where a quantum dialogue protocol is adopted to authenticate the identity of the parties. The participants simultaneously authenticate the identity of each other based on parts of a prior shared key. Moreover, the whole prior shared key can be reused for deducing the secret data. Although the proposed scheme does not significantly improve the efficiency performance, it is more secure compared to some existing quantum secret sharing scheme due to the identity authentication process. In addition, the proposed scheme can stand against participant attack, man-in-the-middle attack, impersonation attack, Trojan-horse attack as well as information leaks.
Neoproterozoic basement history of Wrangel Island and Arctic Chukotka: integrated insights from zircon U–Pb, O and Hf isotopic studies
Authors: Gottlieb Eric S. , Pease Victoria , Miller Elizabeth L. , Akinin Vyacheslav V.
Published: May 2017

The pre-Cenozoic kinematic and tectonic history of the Arctic Alaska Chukotka (AAC) terrane is not well known. The difficulties in assessing the history of the AAC terrane are predominantly due to a lack of comprehensive knowledge about the composition and age of its basement. During the Mesozoic, the AAC terrane was involved in crustal shortening, followed by magmatism and extension with localized high-grade metamorphism and partial melting, all of which obscured its pre-orogenic geological relationships. New zircon geochronology and isotope geochemistry results from Wrangel Island and western Chukotka basement rocks establish and strengthen intra- and inter-terrane lithological and tectonic correlations of the AAC terrane. Zircon U–Pb ages of five granitic and one volcanic sample from greenschist facies rocks on Wrangel Island range between 620±6 and 711±4 Ma, whereas two samples from the migmatitic basement of the Velitkenay massif near the Arctic coast of Chukotka yield 612±7 and 661±11 Ma ages. The age spectrum (0.95–2.0 Ga with a peak at 1.1 Ga and minor 2.5–2.7 Ga) and trace element geochemistry of inherited detrital zircons in a 703±5 Ma granodiorite on Wrangel Island suggests a Grenville–Sveconorwegian provenance for metasedimentary strata in the Wrangel Complex basement and correlates with the detrital zircon spectra of strata from Arctic Alaska and Pearya. Temporal patterns of zircon inheritance and O–Hf isotopes are consistent with Cryogenian–Ediacaran AAC magmatism in a peripheral/external orogenic setting (i.e. a fringing arc on rifted continental margin crust).
Estradiol activates chloride channels via estrogen receptor-α in the cell membranes of osteoblasts
Authors: Deng Zhiqin , Peng Shuang , Zheng Yanfang , Yang Xiaoya , Zhang Haifeng , Tan Qiuchan , Liang Xiechou , Gao Hong , Li Yuan , Huang Yanqing , Zhu Linyan , Jacob Tim J. C. , Chen Lixin , Wang Liwei
Published: May 2017

Estrogen plays important roles in regulation of bone formation. Cl− channels in the ClC family are expressed in osteoblasts and are associated with bone physiology and pathology, but the relationship between Cl− channels and estrogen is not clear. In this study the action of estrogen on Cl− channels was investigated in the MC3T3-E1 osteoblast cell line. Our results show that 17β-estradiol could activate a current that reversed at a potential close to the Cl− equilibrium potential, with a sequence of anion selectivity of I− > Br− > Cl− > gluconate, and was inhibited by the Cl− channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoate and 4,4′-diisothiocyano-2,2′-stilbene disulfonic acid. Knockdown of ClC-3 Cl− channel expression by a specific small interfering RNA to ClC-3 attenuated activation of the 17β-estradiol-induced Cl− current. Extracellular application of membrane-impermeable 17β-estradiol-albumin conjugates activated a similar current. The estrogen-activated Cl− current could be inhibited by the estrogen receptor (ER) antagonist fulvestrant (ICI 182780). The selective ERα agonist, but not ERβ agonist, activated a Cl− current similar to that induced by 17β-estradiol. Silencing ERα expression prevented activation of estrogen-induced currents. Immunofluorescence and coimmunoprecipitation experiments demonstrated that ClC-3 Cl− channels and ERα were colocalized and closely related in cells. Estrogen promoted translocation of ClC-3 and ERα to the cell membrane from the nucleus. In conclusion, our findings show that Cl− channels can be activated by estrogen via ERα on the cell membrane and suggest that the ClC-3 Cl− channel may be one of the targets of estrogen in the regulation of osteoblast activity.
CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma
Authors: Wadkin James C. R. , Patten Daniel A. , Kamarajah Sivesh K. , Shepherd Emma L. , Novitskaya Vera , Berditchevski Fedor , Adams David H. , Weston Chris J. , Shetty Shishir
Published: May 2017

CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention.

NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated in chronic liver disease and hepatocellular carcinoma (HCC) and is regulated on endothelium by tissue remodeling and procarcinogenic factors. These regulatory and functional studies identify CD151 as a potential therapeutic target to treat liver fibrosis and HCC.
Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease
Authors: Wysocki Jan , Goodling Anne , Burgaya Mar , Whitlock Kathryn , Ruzinski John , Batlle Daniel , Afkarian Maryam
Published: May 2017

The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13–20 wk after treatment with streptozotocin ( n = 9) or vehicle ( n = 15) and people with long-standing type 1 diabetes, with ( n = 37) or without ( n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively ( P < 0.001). Enzymatic activities of ACE, ACE2, and APA were 6.2-, 3.2-, and 18.8-fold higher, respectively, in diabetic animals ( P < 0.001). Angiotensin II was 2.4-fold higher in diabetic animals ( P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 109RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy.
Ovariectomy uncovers purinergic receptor activation of endothelin-dependent natriuresis
Authors: Gohar Eman Y. , Kasztan Malgorzata , Becker Bryan K. , Speed Joshua S. , Pollock David M.
Published: May 2017

We recently reported that natriuresis produced by renal medullary salt loading is dependent on endothelin (ET)-1 and purinergic (P2) receptors in male rats. Because sex differences in ET-1 and P2 signaling have been reported, we decided to test whether ovarian sex hormones regulate renal medullary ET-1 and P2-dependent natriuresis. The effect of medullary NaCl loading on Na+excretion was determined in intact and ovariectomized (OVX) female Sprague-Dawley rats with and without ET-1 or P2 receptor antagonism. Isosmotic saline (284 mosmol/kgH2O) was infused in the renal medullary interstitium of anesthetized rats during a baseline urine collection period, followed by isosmotic or hyperosmotic saline (1,800 mosmol/kgH2O) infusion. Medullary NaCl loading significantly enhanced Na+excretion in intact and OVX female rats. ETA+Bor P2 receptor blockade did not attenuate the natriuretic effect of medullary NaCl loading in intact females, whereas ETA+Bor P2 receptor blockade attenuated the natriuretic response to NaCl loading in OVX rats. Activation of medullary P2Y2and P2Y4receptors by UTP infusion had no significant effect in intact females but enhanced Na+excretion in OVX rats. Combined ETA+Breceptor blockade significantly inhibited the natriuretic response to UTP observed in OVX rats. These data demonstrate that medullary NaCl loading induces ET-1 and P2-independent natriuresis in intact females. In OVX, activation of medullary P2 receptors promotes ET-dependent natriuresis, suggesting that ovarian hormones may regulate the interplay between the renal ET-1 and P2 signaling systems to facilitate Na+excretion.
Cell-specific qRT-PCR of renal epithelial cells reveals a novel innate immune signature in murine collecting duct
Authors: Saxena Vijay , Hains David S. , Ketz John , Chanley Melinda , Spencer John D. , Becknell Brian , Pierce Keith R. , Nelson Raoul D. , Purkerson Jeffrey M. , Schwartz George J. , Schwaderer Andrew L.
Published: May 2017

The urinary tract is usually culture negative despite its close proximity to microbial flora. The precise mechanism by which the kidneys and urinary tract defends against infection is not well understood. The initial kidney cells to encounter ascending pathogens are the collecting tubule cells that consist of principal cells (PCs) that express aquaporin 2 (AQP2) and intercalated cells (ICs) that express vacuolar H+-ATPase (V-ATPase, B1 subunit). We have previously shown that ICs are involved with the human renal innate immune defense. Here we generated two reporter mice, VATPase B1-cre+tdT+mice to fluorescently label ICs and AQP2-cre+tdT+mice to fluorescently label PCs, and then performed flow sorting to enrich PCs and ICs for analysis. Isolated ICs and PCs along with proximal tubular cells were used to measure antimicrobial peptide (AMP) mRNA expression. ICs and PCs were significantly enriched for AMPs. Isolated ICs responded to uropathogenic Escherichia coli (UPEC) challenge in vitro and had higher RNase4 gene expression than control while both ICs and PCs responded to UPEC challenge in vivo by upregulating Defb1 mRNA expression. To our knowledge, this is the first report of isolating murine collecting tubule cells and performing targeted analysis for multiple classes of AMPs.
Circuit feedback increases activity level of a circuit input through interactions with intrinsic properties
Authors: Blitz Dawn M.
Published: May 2017

Feedback from central pattern generator (CPG) circuits patterns activity of their projection neuron inputs. However, whether the intraburst firing rate between rhythmic feedback inhibition is also impacted by CPG feedback was not known. I establish that CPG feedback can alter the projection neuron intraburst firing rate through interactions with projection neuron intrinsic properties. The contribution of feedback to projection neuron activity level is specific to the modulatory condition, demonstrating a state dependence for this novel role of circuit feedback.
Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells
Authors: McFarland A. J. , Davey A. K. , Anoopkumar-Dukie S.
Published: May 2017

The anti-inflammatory effects of statins (HMG-CoA reductase inhibitors) within the cardiovascular system are well-established; however, their neuroinflammatory potential is unclear. It is currently unknown whether statins’ neurological effects are lipid-dependent or due to pleiotropic mechanisms. Therefore, the assumption that all statin compounds will have the same effect within the central nervous system is potentially inappropriate, with no studies to date having compared all statins in a single model. Thus, the aim of this study was to compare the effects of the six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) within a single in vitro model of neuroinflammation. To achieve this, PMA-differentiated THP-1 cells were used as surrogate microglial cells, and LPS was used to induce inflammatory conditions. Here, we show that pretreatment with all statins was able to significantly reduce LPS-induced interleukin (IL)-1βand tumour necrosis factor (TNF)-αrelease, as well as decrease LPS-induced prostaglandin E2 (PGE2). Similarly, global reactive oxygen species (ROS) and nitric oxide (NO) production were decreased following pretreatment with all statins. Based on these findings, it is suggested that more complex cellular models should be considered to further compare individual statin compounds, including translation into in vivo models of acute and/or chronic neuroinflammation.
Commercial Essential Oils as Potential Antimicrobials to Treat Skin Diseases
Authors: Orchard Ané , van Vuuren Sandy
Published: May 2017

Essential oils are one of the most notorious natural products used for medical purposes. Combined with their popular use in dermatology, their availability, and the development of antimicrobial resistance, commercial essential oils are often an option for therapy. At least 90 essential oils can be identified as being recommended for dermatological use, with at least 1500 combinations. This review explores the fundamental knowledge available on the antimicrobial properties against pathogens responsible for dermatological infections and compares the scientific evidence to what is recommended for use in common layman’s literature. Also included is a review of combinations with other essential oils and antimicrobials. The minimum inhibitory concentration dilution method is the preferred means of determining antimicrobial activity. While dermatological skin pathogens such as Staphylococcus aureus have been well studied, other pathogens such as Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, and Brevibacterium species have been sorely neglected. Combination studies incorporating oil blends, as well as interactions with conventional antimicrobials, have shown that mostly synergy is reported. Very few viral studies of relevance to the skin have been made. Encouragement is made for further research into essential oil combinations with other essential oils, antimicrobials, and carrier oils.
Study of Guanxinning Injection on Regulatory Mechanism of Bcl‐2 and Bax by Liquid Nitrogen Freezing‐Mediated Femoral Head Necrosis
Authors: Zhang Xiaofeng , Xu Xilin , Litscher Gerhard , Sheng Zemin , Wang Lu , Litscher Daniela , Lv Hang , Li Xiaodong , Zhang Jie , Su Hui , Liu Peiran , Hu Hai
Published: May 2017

The objective of this study was to investigate the impact of femoral head perfusion by traditional Chinese medicine Guanxinning injection promoting blood circulation for removing blood stasis on the expression of Bcl‐2 and Bax induced by liquid nitrogen freezing‐mediated femoral head necrosis. 90 rabbits were randomized into three groups. Normal control group was not subjected to any medication. Saline and Guanxinning group were perfused with 0.9% saline and Guanxinning injection once every three days through the hip joint, respectively. Six animals in each group were sacrificed at weeks 1, 3, 6, 9, and 12. PCR and Western blot measured the expressions of Bcl‐2 and Bax in the femoral head. The bax expression in the Guanxinning group reduced at the third week significantly compared to the normal control group (P < 0.01). The Bcl‐2 expression in the Guanxinning group increased substantially at the third week (P < 0.05 or P < 0.01). Prolonged treatment elevated the expression of Bcl‐2 in the Guanxinning group while that of Bax reduced remarkably (P < 0.01). Moreover, the ratio of Bcl‐2 to Bax increased gradually in the Guanxinning group with prolonged drug administration. Guanxinning injection can inhibit the cell apoptosis of femoral head necrosis through the treatment by femoral head perfusion.
Water Content Influence on Properties of Red-Layers in Guangzhou Metro Line, China
Authors: Liu Jifeng , Zhang Huizhi
Published: May 2017

In order to reveal water content influence on shear strength, swelling, and creep properties of red-layers in Guangzhou Metro, Southern China, the typical red-layers rock and soil specimens were experimentally studied by direct shear test, UU triaxial test, swelling test, and creep test, and the measured data were analyzed. The results showed that soil internal friction angle exponentially decreased with the water content increase and cohesion in accordance with the Gaussian function firstly increased and then decreased with the increase of water content. Expansion rate significantly decreased with the initial water content increase. The red sandstone had very strong isotropic expansion and disintegration properties. The mechanism of water content effect on red-layers properties was water induced microstructures and mineral compositions change which caused the macro physical and mechanical characteristics degradation. The results should provide the reference for further research for water induced damage mechanism or creep damage control of red-layers in engineering practice.
Ribonuclease fromBacillusActs as an Antiviral Agent against Negative- and Positive-Sense Single Stranded Human Respiratory RNA Viruses
Authors: Shah Mahmud Raihan , Müller Christin , Romanova Yulia , Mostafa Ahmed , Ulyanova Vera , Pleschka Stephan , Ilinskaya Olga
Published: May 2017

Bacillus pumilusribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectively, which annually cause respiratory illnesses and are characterized by high contagious nature, mutation rate, and antigen variability. We have shown that binase exerts an antiviral effect on both viruses at the same concentration, which does not alter the spectrum of A549 cellular proteins and expression of housekeeping genes. The titers of influenza A (H1N1pdm) virus and human rhinovirus serotype 1A were reduced by 40% and 65%, respectively. A preincubation of influenza virus with binase before infection significantly reduced viral titer after single-cycle replication of the virus. Using influenza A virus mini genome system we showed that binase reduced GFP reporter signaling indicating a binase action on the expression of viral mRNA. Binase reduced the level of H1N1pdm viral NP mRNA accumulation in A549 cells by 20%. Since the viral mRNA is a possible target for binase this agent could be potentially applied in the antiviral therapy against both negative- and positive-sense RNA viruses.
Comparison of Brain Activation during Motor Imagery and Motor Movement Using fNIRS
Authors: Batula Alyssa M. , Mark Jesse A. , Kim Youngmoo E. , Ayaz Hasan
Published: May 2017

Motor-activity-related mental tasks are widely adopted for brain-computer interfaces (BCIs) as they are a natural extension of movement intention, requiring no training to evoke brain activity. The ideal BCI aims to eliminate neuromuscular movement, making motor imagery tasks, or imagined actions with no muscle movement, good candidates. This study explores cortical activation differences between motor imagery and motor execution for both upper and lower limbs using functional near-infrared spectroscopy (fNIRS). Four simple finger- or toe-tapping tasks (left hand, right hand, left foot, and right foot) were performed with both motor imagery and motor execution and compared to resting state. Significant activation was found during all four motor imagery tasks, indicating that they can be detected via fNIRS. Motor execution produced higher activation levels, a faster response, and a different spatial distribution compared to motor imagery, which should be taken into account when designing an imagery-based BCI. When comparing left versus right, upper limb tasks are the most clearly distinguishable, particularly during motor execution. Left and right lower limb activation patterns were found to be highly similar during both imagery and execution, indicating that higher resolution imaging, advanced signal processing, or improved subject training may be required to reliably distinguish them.
Research on Trajectory Planning and Autodig of Hydraulic Excavator
Authors: Zhang Bin , Wang Shuang , Liu Yuting , Yang Huayong
Published: May 2017

As the advances in computer control technology keep emerging, robotic hydraulic excavator becomes imperative. It can improve excavation accuracy and greatly reduce the operator’s labor intensity. The 12‐ton backhoe bucket excavator has been utilized in this research work where this type of excavator is commonly used in engineering work. The kinematics model of operation device (boom, arm, bucket, and swing) in excavator is established in both Denavit‐Hartenberg coordinates for easy programming and geometric space for avoiding blind spot. The control approach is based on trajectory tracing method with displacements and velocities feedbacks. The trajectory planning and autodig program is written by Visual C++. By setting the bucket teeth’s trajectory, the program can automatically plan the velocity and acceleration of each hydraulic cylinder and motor. The results are displayed through a 3D entity simulation environment which can present real‐time movements of excavator kinematics. Object‐Oriented Graphics Rendering Engine and skeletal animation are used to give accurate parametric control and feedback. The simulation result shows that a stable linear autodig can be achieved. The errors between trajectory planning command and simulation model are analyzed.
Caveolin‐1: An Oxidative Stress‐Related Target for Cancer Prevention
Authors: Wang Shengqi , Wang Neng , Zheng Yifeng , Zhang Jin , Zhang Fengxue , Wang Zhiyu
Published: May 2017

Aberrant oxidative metabolism is one of the hallmarks of cancer. Reactive species overproduction could promote carcinogenesis via inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy was considered as an important strategy for cancer prevention and treatment. Caveolin‐1 (Cav‐1), a constituent protein of caveolae, has been shown to mediate tumorigenesis and progression through oxidative stress modulation recently. Reactive species could modulate the expression, degradation, posttranslational modifications, and membrane trafficking of Cav‐1, while Cav‐1‐targeted treatments could scavenge the reactive species. More importantly, emerging evidences have indicated that multiple antioxidants could exert antitumor activities in cancer cells and protective activities in normal cells by modulating the Cav‐1 pathway. Altogether, these findings indicate that Cav‐1 may be a promising oxidative stress‐related target for cancer antioxidant prevention. Elucidating the underlying interaction mechanisms between oxidative stress and Cav‐1 is helpful for enhancing the preventive effects of antioxidants on cancer, for improving clinical outcomes of antioxidant‐related therapeutics in cancer patients, and for developing Cav‐1 targeted drugs. Herein, we summarize the available evidence of the roles of Cav‐1 and oxidative stress in tumorigenesis and development and shed novel light on designing strategies for cancer prevention or treatment by utilizing the interaction mode between Cav‐1 and oxidative stress.
A Collection‐Distribution Center Location and Allocation Optimization Model in Closed‐Loop Supply Chain for Chinese Beer Industry
Authors: Kang Kai , Wang Xiaoyu , Ma Yanfang
Published: May 2017

Recycling waste products is an environmental‐friendly activity that can result in manufacturing cost saving and economic efficiency improving. In the beer industry, recycling bottles can reduce manufacturing cost and the industry’s carbon footprint. This paper presents a model for a collection‐distribution center location and allocation problem in a closed‐loop supply chain for the beer industry under a fuzzy random environment, in which the objectives are to minimize total costs and transportation pollution. Both random and fuzzy uncertainties, for which return rate and disposal rate are considered fuzzy random variables, are jointly handled in this paper to ensure a more practical problem solution. A heuristic algorithm based on priority‐based global‐local‐neighbor particle swarm optimization (pb‐glnPSO) is applied to ensure reliable solutions for this NP‐hard problem. A beer company case study is given to illustrate the application of the proposed model and to demonstrate the priority‐based global‐local‐neighbor particle swarm optimization.
Effect of Frying Treatments on Texture and Colour Parameters of Deep Fat Fried Yellow Fleshed Cassava Chips
Authors: Oyedeji A. B. , Sobukola O. P. , Henshaw Folake , Adegunwa M. O. , Ijabadeniyi O. A. , Sanni L. O. , Tomlins K. I.
Published: May 2017

Effects of frying treatments on texture (hardness) and colour parameters (L,a,b,ΔE) during deep fat frying of yellow fleshed cassava root slices (TMS 01/1371) were investigated. Slices (dimension of 40 mm × 25 mm × 3 mm) were divided into three portions and subjected to vacuum frying (fresh slices) and atmospheric frying (fresh and predried slices) and equivalent thermal driving forces (ETDF) of 60°C, 70°C, and 80°C were maintained during frying. The quality attributes investigated were best preserved in vacuum fried chips. The overall colour change in chips fried under vacuum conditions at 118°C and 8 min was the least (21.20) compared to fresh and atmospherically predried ones (16.69 and 14.81, resp.). A sharp reduction in the breaking force was obtained for all frying treatments after 8 min and this effect was the least in vacuum fried chips. First-order kinetics modeled the changes in quality attributes for all the temperatures investigated. Rate constants k (min−1) obtained for vacuum frying were almost equal to that of atmospheric frying while activation energies for hardness and colour change were 53.30 and 467.11 KJ/mol, respectively. Quality attributes studied were best preserved during vacuum frying.
The Adaptive-Clustering and Error-Correction Method for Forecasting Cyanobacteria Blooms in Lakes and Reservoirs
Authors: Bai Xiao-zhe , Zhang Hui-yan , Wang Xiao-yi , Wang Li , Xu Ji-ping , Yu Jia-bin
Published: May 2017

Globally, cyanobacteria blooms frequently occur, and effective prediction of cyanobacteria blooms in lakes and reservoirs could constitute an essential proactive strategy for water-resource protection. However, cyanobacteria blooms are very complicated because of the internal stochastic nature of the system evolution and the external uncertainty of the observation data. In this study, an adaptive-clustering algorithm is introduced to obtain some typical operating intervals. In addition, the number of nearest neighbors used for modeling was optimized by particle swarm optimization. Finally, a fuzzy linear regression method based on error-correction was used to revise the model dynamically near the operating point. We found that the combined method can characterize the evolutionary track of cyanobacteria blooms in lakes and reservoirs. The model constructed in this paper is compared to other cyanobacteria-bloom forecasting methods (e.g., phase space reconstruction and traditional-clustering linear regression), and, then, the average relative error and average absolute error are used to compare the accuracies of these models. The results suggest that the proposed model is superior. As such, the newly developed approach achieves more precise predictions, which can be used to prevent the further deterioration of the water environment.
Endothelial Alterations in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Potential Effect of Monocyte Interaction
Authors: Atehortúa Laura , Rojas Mauricio , Vásquez Gloria M. , Castaño Diana
Published: May 2017

Patients with systemic autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are prone to develop atherosclerosis and cardiovascular diseases five times more often than the general population; this increase in frequency could be partially explained by an increase in the macrovasculature endothelial damage. In these autoimmune diseases, a microvascular endothelial injury has also been reported in different organs and tissues, especially in sites where ultrafiltration processes occur. Different components that are characteristic to the immunopathology of RA and SLE could be involved in the endothelial cell activation, permeability increase, functional alteration, and vascular injury. Circulating immune complexes (IC) detected in SLE and RA have been proposed to participate in the endothelial injury. In the vascular environment, IC can generate different responses that could be mediated by monocytes, because these cells have patrolling and monitoring functions on the endothelium. However, with certain stimuli such as TLR ligands, the monocytes are retained in the lumen, releasing proinflammatory mediators that participate in the endothelial damage. This paper aims to review some aspects about the endothelial activation and dysfunction in the context of SLE and RA, as well as the potential role that monocytes apparently play in this process.
Modeling of Patient-Derived Xenografts in Colorectal Cancer
Authors: Katsiampoura Anastasia , Raghav Kanwal , Jiang Zhi-Qin , Menter David G. , Varkaris Andreas , Morelli Maria P. , Manuel Shanequa , Wu Ji , Sorokin Alexey V. , Rizi Bahar Salimian , Bristow Christopher , Tian Feng , Airhart Susan , Cheng Mingshan , Broom Bradley M. , Morris Jeffrey , Overman Michael J. , Powis Garth , Kopetz Scott
Published: May 2017

Developing realistic preclinical models using clinical samples that mirror complex tumor biology and behavior are vital to advancing cancer research. While cell line cultures have been helpful in generating preclinical data, the genetic divergence between these and corresponding primary tumors has limited clinical translation. Conversely, patient-derived xenografts (PDX) in colorectal cancer are highly representative of the genetic and phenotypic heterogeneity in the original tumor. Coupled with high-throughput analyses and bioinformatics, these PDXs represent robust preclinical tools for biomarkers, therapeutic target, and drug discovery. Successful PDX engraftment is hypothesized to be related to a series of anecdotal variables namely, tissue source, cancer stage, tumor grade, acquisition strategy, time to implantation, exposure to prior systemic therapy, and genomic heterogeneity of tumors. Although these factors at large can influence practices and patterns related to xenotransplantation, their relative significance in determining the success of establishing PDXs is uncertain. Accordingly, we systematically examined the predictive ability of these factors in establishing PDXs using 90 colorectal cancer patient specimens that were subcutaneously implanted into immunodeficient mice. Fifty (56%) PDXs were successfully established. Multivariate analyses showed tissue acquisition strategy [surgery 72.0% (95% confidence interval (CI): 58.2–82.6) vs. biopsy 35% (95% CI: 22.1%–50.6%)] to be the key determinant for successful PDX engraftment. These findings contrast with current empiricism in generating PDXs and can serve to simplify or liberalize PDX modeling protocols. Better understanding the relative impact of these factors on efficiency of PDX formation will allow for pervasive integration of these models in care of colorectal cancer patients. Mol Cancer Ther; 16(7); 1435–42. ©2017 AACR.
The Multi-kinase Inhibitor Debio 0617B Reduces Maintenance and Self-renewal of Primary Human AML CD34+ Stem/Progenitor Cells
Authors: Murone Maximilien , Radpour Ramin , Attinger Antoine , Chessex Anne Vaslin , Huguenin Anne-Laure , Schürch Christian M. , Banz Yara , Sengupta Saumitra , Aguet Michel , Rigotti Stefania , Bachhav Yogeshwar , Massière Frédéric , Ramachandra Murali , McAllister Andres , Riether Carsten
Published: May 2017

Acute myelogenous leukemia (AML) is initiated and maintained by leukemia stem cells (LSC). LSCs are therapy-resistant, cause relapse, and represent a major obstacle for the cure of AML. Resistance to therapy is often mediated by aberrant tyrosine kinase (TK) activation. These TKs primarily activate downstream signaling via STAT3/STAT5. In this study, we analyzed the potential to therapeutically target aberrant TK signaling and to eliminate LSCs via the multi-TK inhibitor Debio 0617B. Debio 0617B has a unique profile targeting key kinases upstream of STAT3/STAT5 signaling such as JAK, SRC, ABL, and class III/V receptor TKs. We demonstrate that expression of phospho-STAT3 (pSTAT3) in AML blasts is an independent prognostic factor for overall survival. Furthermore, phospho-STAT5 (pSTAT5) signaling is increased in primary CD34+ AML stem/progenitors. STAT3/STAT5 activation depends on tyrosine phosphorylation, mediated by several upstream TKs. Inhibition of single upstream TKs did not eliminate LSCs. In contrast, the multi-TK inhibitor Debio 0617B reduced maintenance and self-renewal of primary human AML CD34+ stem/progenitor cells in vitro and in xenotransplantation experiments resulting in long-term elimination of human LSCs and leukemia. Therefore, inhibition of multiple TKs upstream of STAT3/5 may result in sustained therapeutic efficacy of targeted therapy in AML and prevent relapses. Mol Cancer Ther; 16(8); 1497–510. ©2017 AACR.
Sildenafil Suppresses Inflammation-Driven Colorectal Cancer in Mice
Authors: Islam Bianca N. , Sharman Sarah K. , Hou Yali , Bridges Allison E. , Singh Nagendra , Kim Sangmi , Kolhe Ravindra , Trillo-Tinoco Jimena , Rodriguez Paulo C. , Berger Franklin G. , Sridhar Subbaramiah , Browning Darren D.
Published: May 2017

Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against dextran-sulfate sodium (DSS)-induced barrier dysfunction. In mice treated with AOM/DSS, oral administration of sildenafil throughout the disease course reduced polyp multiplicity by 50% compared with untreated controls. Polyps that did form in sildenafil treated mice were less proliferative and more differentiated compared with polyps from untreated mice, but apoptosis was unaffected. Polyps in sildenafil treated mice were also less inflamed; they exhibited reduced myeloid-cell infiltration and reduced expression of iNOS, IFNγ, and IL6 compared with untreated controls. Most of the protection conferred by sildenafil was during the initiation stage of carcinogenesis (38% reduction in multiplicity). Administration of sildenafil during the later promotion stages did not affect multiplicity but had a similar effect on the polyp phenotype, including increased mucus production, and reduced proliferation and inflammation. In summary, the results demonstrate that oral administration of sildenafil suppresses polyp formation and inflammation in mice treated with AOM/DSS. This validation of PDE5 as a target highlights the potential therapeutic value of PDE5 inhibitors for the prevention of colitis-driven colon cancer in humans. Cancer Prev Res; 10(7); 377–88. ©2017 AACR.

See related editorial by Piazza, p. 373.
Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats
Authors: Ma Rufeng , Wang Lili , Zhao Baosheng , Liu Chenyue , Liu Haixia , Zhu Ruyuan , Chen Beibei , Li Lin , Zhao Dandan , Mo Fangfang , Li Yu , Niu Jianzhao , Jiang Guangjian , Fu Min , Bromme Dieter , Gao Sihua , Zhang Dongwei
Published: May 2017

Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats.
Early- versus Late-Onset Alzheimer Disease: Long-Term Functional Outcomes, Nursing Home Placement, and Risk Factors for Rate of Progression
Authors: Wattmo Carina , Wallin Åsa K.
Published: May 2017

Background/Aims: Whether age at onset influences functional deterioration in Alzheimer disease (AD) is unclear. We, therefore, investigated risk factors for progression in activities of daily living (ADL) and nursing home placement (NHP) in cholinesterase inhibitor (ChEI)-treated patients with early-onset AD (EOAD) versus late-onset AD (LOAD). Methods: This 3-year, prospective, observational, multicenter study included 1,017 participants with mild-to-moderate AD; 143 had EOAD (onset <65 years) and 874 LOAD (onset ≥65 years). Possible sociodemographic and clinical factors that could affect functional outcome and NHP were analyzed using mixed-effects models and logistic regression, respectively. Results: Younger individuals exhibited longer illness duration before AD diagnosis, whereas 6-month functional response to ChEI therapy, 3-year changes in ADL capacities, time from diagnosis to NHP, and survival time in nursing homes were similar between the groups. In LOAD, a higher ChEI dose, no antidepressant use, and lower education level were protective factors for slower instrumental ADL (IADL) decline. In EOAD, antihypertensives/cardiac therapy implied faster IADL progression but lower risk of NHP. Conclusion: This study highlights the clinical importance of an earlier diagnosis and treatment initiation and the need for functional evaluations in EOAD. Despite the age differences between EOAD and LOAD, a similar need for nursing homes was observed.
Inhibition of TRPC6 Signal Pathway Alleviates Podocyte Injury Induced by TGF-β1
Authors: Huang Haiting , You Yanwu , Lin Xu , Tang Chunrong , Gu Xiangjun , Huang Meiying , Qin Youling , Tan Junhua , Huang Feifan
Published: May 2017

Background/Aims: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of transient receptor potential cation channel C6 (TRPC6) on podocyte injury induced by TGF-β1 via nephrin and desmin mechanisms. Methods: A rat model of nephropathy was first induced by intravenous injections of adriamycin to determine TRPC6 signal pathway engaged in glomerulosclerosis in vivo. Conditionally immortalized podocytes were cultured in vitro and they were divided into four groups: control; TGF-β1 treatment; TGF-β1 with TRPC6 knockdown and TGF-β1 without TRPC6 knockdown. Real time RT-PCR and Western blot analysis were employed to determine the mRNA and protein of expression of nephrin, desmin and caspase-9, respectively. Flow cytometry was used to examine the apoptotic rate of podocytes and DAPI fluorescent staining was used to determine apoptotic morphology. Results: In vivo experiment, adriamycin significantly upregulated the protein expression of TGF-β1, TRPC6, desmin and caspase-9, and decreased nephrin. Consistent with the latter results, in vitro experiment mRNA and protein expression of desmin and caspase-9 was increased in cultured TGF-β1-treated podocytes, whereas nephrin was declined as compared with the control group. Importantly, TRPC6 knockdown significantly attenuated the upregulated desmin and caspase-9, and alleviated impairment of nephrin induced by TGF-β1. Moreover, typical morphologic features were presented in apoptotic podocytes. The number of apoptotic podocytes was increased after exposure to TGF-β1 and this was alleviated after TRPC6 knockdown. TRPC6 knockdown also decreased an apoptosis rate of TGF-β1-treated podocytes. Note that negative TRPC6 transfection control failed to alter an increase of the apoptosis rate in TGF-β1-treated podocytes. Conclusions: TGF-β1 induced by glomerulosclerosis impairs the protein expression of nephrin and amplifies the protein expression of desmin and caspase -9 via TRPC6 signal pathway. Inhibition of TRPC6 alleviates these changes in podocytes-treated with TGF-β1 and attenuated apoptosis of podocytes. Our data suggest that TRPC6 signal plays an important role in mediating TGF-β1-induced podocyte injury via nephrin, desmin and caspase-9. Results of the current study also indicate that blocking TRPC6 signal pathway has a protective effect on podocyte injury. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of podocyte injury observed in glomerulosclerosis.
Efficacy and Safety of MLC601 in the Treatment of Mild Cognitive Impairment: A Pilot, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Pakdaman Hossein , Amini Harandi Ali , Abbasi Mehdi , Delavar Kasmaei Hosein , Ashrafi Farzad , Gharagozli Koroush , Assarzadegan Farhad , Behnam Behdad , Arabahmadi Mehran
Published: May 2017

Background and Aim: Mild cognitive impairment (MCI) is characterized by declined cognitive function greater than that expected for a person’s age. The clinical significance of this condition is its possible progression to dementia. MLC601 is a natural neuroprotective medication that has shown promising effects in Alzheimer disease. Accordingly, we conducted this randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of MLC601 in MCI patients. Methods: Seventy-two patients with a diagnosis of MCI were recruited. The included participants were randomly assigned to groups to receive either MLC601 or placebo. An evaluation of global cognitive function was performed at baseline as well as at 3-month and 6-month follow-up visits. Global cognitive function was assessed by Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) scores. Efficacy was evaluated by comparing global function scores between the 2 groups during the study period. Safety assessment included adverse events (AEs) and abnormal laboratory results. Results: Seventy patients completed the study, 34 in the MLC601 group and 36 in the placebo group. The mean changes (±SD) in cognition scores over 6 months in the MLC601 group were –2.26 (±3.42) for the MMSE and 3.82 (±6.16) for the ADAS-cog; in the placebo group, they were –2.66 (±3.43) for the MMSE and 4.41 (±6.66) for the ADAS-cog. The cognition changes based on both MMSE and ADAS-cog scores were statistically significant between the placebo and the MLC601 group (p < 0.001). Only 5 patients (14.7%) reported minor AEs in the MLC601 group, the most commonly reported of which were gastrointestinal, none of them leading to patient withdrawal. Conclusion: MLC601 has shown promising efficacy and acceptable AEs in MCI patients.
YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription
Authors: Fan Ye , Gao Yangjuan , Rao Jianhua , Wang Ke , Zhang Feng , Zhang Chuanyong
Published: May 2017

Background/Aims: Immunosuppression is one of the hallmarks of cancer; however, its molecular mechanism remains unknown. In the present study, we sought to investigate the expression and activation of yes-associated protein 1 (YAP-1) and its roles in T cells within hepatocellular carcinoma (HCC). Methods: The expression and activation of YAP-1 were accessed by real-time PCR, immunohistochemistry staining, western blot, and flow cytometry. The potential regulation effect of YAP-1 on Regulatory T cells (Tregs) differentiation was predicted using bioinformatics tools and verified by in vitro studies. Results: Significant overexpression and activation of YAP-1 was detected within peripheral blood mononuclear cells and showed positive linear correlation to Treg percentage; it may serve as a valuable indicator of a bad prognosis. Using in vitro studies, we found that overexpression and activation of YAP-1 can promote naïve T cell polarization stimulation to Tregs by increasing the expression of TGFBR2. The YAP-1/TEADs DNA binding site was spotted within the promoter region of TGFBR2 and related to its transcription activity. YAP-1 acted as a co-activator of TGFBR2 transcription by binding directly to the TGFBR2 promoter through TEADs. Conclusion: Overexpression and activation of YAP-1 in HCC T cells can induce immunosuppression by promoting Treg differentiation via transcriptional enhancement of TGFBR2.