bluuebunny/crossref_metadata_2025 huggingface dataset:
Arc/Arg3.1 defines dendritic cells and Langerhans cells with superior migratory ability independent of phenotype and ontogeny in mice
Authors: Tintelnot Joseph , Ufer Friederike , Engler Jan Broder , Winkler Hana , Lücke Karsten , Mittrücker Hans‐Willi , Friese Manuel A.
Published: February 2019

The key function of migratory dendritic cells (migDCs) is to take up antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate immune responses. Recently, we discovered that in the mouse immune system activity‐regulated cytoskeleton associated protein/activity‐regulated gene 3.1 (Arc/Arg3.1) is exclusively expressed by migDCs and is a central driver of fast inflammatory migration. However, the frequency of Arc/Arg3.1‐expressing cells in different migDC subsets and Langerhans cells (LCs), their phylogenetic origin, transcription factor dependency, and functional role remain unclear. Here, we found that Arc/Arg3.1+ migDCs derived from common DC precursors and radio‐resistant LCs. We detected Arc/Arg3.1+ migDCs in varying frequencies within each migDC subset and LCs. Consistently, they showed superiority in inflammatory migration. Arc/Arg3.1 expression was independent of the transcription factors Irf4 or Batf3 in vivo. In intradermal Staphylococcus aureus infection that relies on inflammatory antigen transport, Arc/Arg3.1 deletion reduced T‐cell responses. By contrast, Arc/Arg3.1 deficiency did not hamper the immune response to systemic Listeria monocytogenes infection, which does not require antigen transport. Thus, Arc/Arg3.1 expression is independent of ontogeny and phenotype and although it is restricted to a small fraction within each migDC subset and LCs, Arc/Arg3.1+ migDCs are important to facilitate infectious migration.
Effect of Ligands on the Lewis Acidity of the Metal and the Binding of N‐Bases to Iridium Pincer Complexes
Authors: Osipova Elena S. , Gulyaeva Ekaterina S. , Filippov Oleg A. , Safronov Sergey V. , Pavlov Alexander A. , Polukeev Alexey V. , Kirkina Vladislava A. , Titova Ekaterina M. , Shubina Elena S. , Belkova Natalia V.
Published: February 2019

The coordination of pyridine (Py) and benzonitrile (PhCN) to benzene based pincer hydridochlorides [(PCP)IrH(Cl)] (1), [(POCOP)IrH(Cl)] (2), [{EtO(O)C‐POCOP}IrH(Cl)] (3), and [(PCN)IrH(Cl)] (4) was studied spectroscopically and computationally to deduce the ligand influence. The variable temperature NMR (1H, 31P, 15N) and UV/Visible spectroscopic measurements revealed preferential coordination of these N‐donor ligands in the apical position of 1–4 and gave the formation enthalpies for the hexacoordinate complexes, which follow the order: 1 ≈ 4 > 3 > 2. This order nicely agrees with the order of Lewis acidity obtained for these complexes in DFT calculations. The orbital and electron density distribution analysis were performed at the DFT/M06 theory level for 1–4 and a series of p‐substituted PCP‐based hydridochlorides. The increasing Lewis acidity of iridium [as a maximum energy, VS,max, of molecular electrostatic potential (MEP)] correlates with decreasing basicity of Cl‐ligand (as MEP minimum, VS,min) as well as with Hammett σp parameters of p‐substituents. Importantly, these properties are conserved upon conversion into the corresponding dihydrides, as shown on the example of 1 and 4.
Borohydride as Magnetic Superexchange Pathway in Late Lanthanide Borohydrides
Authors: Wegner Wojciech , van Leusen Jan , Majewski Jacek , Grochala Wojciech , Kögerler Paul
Published: February 2019

The magnetic characteristics of a series of borohydride‐based systems, including binary α‐/β‐Ln(BH4)3 phases (Ln = Gd, Tb, Dy, Ho, Er, and Tm) with direct Ln–HBH–Ln bridges and selected mixed‐metal systems, LiYb(BH4)4, NaYb(BH4)4, KHo(BH4)4, RbTm(BH4)4, with isolated Ln3+ ions embedded in [Ln(BH4)4]– anions are described for the first time using SQUID magnetometry and DFT+U calculations. Crystal field effects as well as the nature and strength of magnetic superexchange interactions via BH4– ligands are established based on a ligand field theory approach. We find Auzel's scalar crystal field strength parameter (Nv, the weighted quadratic mean of the ligand field parameters Bkq) for these systems to be substantial, in particular for α‐Ho(BH4)3, indicating a significant covalent component in the Ho···H bonding. The BH4– anion is capable of mediating both weakly ferro‐ or antiferromagnetic superexchange. Quantum mechanical DFT+U calculations, even when including spin‐orbit coupling effects, do not reliably describe the sign and the size of the magnetic superexchange constants in these systems.
Silver(I)‐Based Complexes Used as High‐Performance Photocatalysts for the Degradation of Organic Dyes in Water
Authors: Liu Chao‐Fan , Liu Chun‐Yu , Ren Zhi‐Gang , Lang Jian‐Ping
Published: February 2019

Coordination compounds have been used as efficient photocatalysts for the degradation of pollutive organic dyes due to their semiconductive nature and diverse structures that may be adjusted by the central metals and ligands. Herein we prepared N′,N′‐2,2‐tetrakis(diphenylphosphanylmethyl)thiocarbohydrazide (tpptch) and utilized it to react with AgX (X = Br, I, CN) in different solvent systems. These reactions afforded two dicationic tetranuclear complexes {[Ag4X2(tpptch)2]X2 (1: X = Br; 2: X = I)}, one 1D coordination polymer [Ag2I2(tpptch)]n (3) and one neutral tetranuclear complex [Ag4(CN)2(dptpptch)2] (4, dptpptch is the anion of deprotonated tpptch after an enolization). In 1–4, the S atom of the C=S group binds at one AgI atom in 1 or 2, or remains uncoordinated in 3, or connects with two AgI atoms after transforming into the C–S– end in 4. The catalytic activities of these compounds toward the photodegradation of nine organic dyes under UV irradiation were examined, among which 3 showed the best performance. Their anodic photocurrent responses and HOMO–LUMO energy gaps derived from density functional theory (DFT) calculations correlated well with the photocatalytic activities. The different bindings of the S end of tpptch and dptpptch ligands with AgI centers in 2–4 may be contributed to the discrepancy in their catalytic activities. The results provide a ready route to design and prepare highly stable and efficient photocatalysts for treating dye‐polluted water.
Illuminating the Intermolecular vs. Intramolecular Excited State Energy Transfer Quenching by Europium(III) Ions
Authors: Junker Anne Kathrine R. , Sørensen Thomas Just
Published: February 2019

InvitedInvited for the cover of this issue are AnneàKathrine Junker and ThomasàJustàSørensen from University of Copenhagen, Denmark. The cover image shows the fireworks of lanthanide luminescence and illustrates that intramolecular excited state energy transfer happens with a rate constant similar to that of the intermolecular process.
Elimination of direct red 264 using magnetic pure and Zn‐doped NiFe2O4 nanophotocatalysts under visible light irradiation: Isothermic and kinetic studies
Authors: Kar Mahnaz Kamel Attar , Fazaeli Reza , Manteghi Faranak , Ghahari Mahdi
Published: February 2019

Photocatalytic degradation of direct red 264 under visible light using NiFe2O4 and Zn‐doped NiFe2O4 nanoparticles was the primary goal of this work. Hence, NiFe2O4 and Zn‐doped NiFe2O4 nanoparticles were prepared by the sol–gel auto combustion method. The powder X‐ray diffraction pattern unveiled the formation of spinel phase of NiFe2O4 with the average crystallite size determined from the Scherrer equation. The FTIR spectra of the samples revealed the vibration bands of Fe–O and Ni–O. The morphology and size of the synthesized nanoparticles have been observed by scanning electron microscopy. The band gap calculated using Kubelka–Munk function from the UV–visible diffuse reflectance spectra. Finally, removal of azo dye and corresponding kinetic and isothermic studies was examined. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13097, 2019
Exergetic environmental sustainability assessment supported by Monte Carlo simulations: A case study of a chlorine production process
Authors: Ghannadzadeh Ali , Tarighaleslami Amir Hossein
Published: February 2019

Chlorine production process can result in discharge of tremendously harmful materials besides it requires high‐energy need, which basically can also lead to additional environmental impacts. This article presents an exergy‐aided life cycle assessment (LCA) to evaluate power generation from natural gas and biomass in the phase of green energy transition to augment the sustainability as much as attainable. A series of statistically discernible scenarios assisted by Monte Carlo Simulation are specified. Results show a reduction in environmental impacts from 2.249E‐02 to 2.180E‐02 MJ‐Eq of nonrenewable energy supplies in accordance with the cumulative exergy demand or from 1.28E‐06 to 7.62E‐07 in accordance with ReCiPe 2008, paving the way toward an environmentally sustainable chlorine production process. LCA is useful to measure the environmental impacts of each chemical constituent accurately, showing that CO2 emitted from this process has much more unfavorable impacts than other harmful materials on human health. Furthermore, LCA discloses that the natural gas could even be less environmentally sustainable than residual fuel oil concerning human toxicity freshwater ecotoxicity, marine ecotoxicity, particulate matter formation, terrestrial acidification, and fossil depletion impacts. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13146, 2019
Combining USGS ShakeMaps and the OpenQuake‐engine for damage and loss assessment
Authors: Silva Vitor , Horspool Nick
Published: February 2019

The evaluation of the potential impact of strong seismic events shortly after their occurrence is a critical step to organise emergency response and consequently minimise the adverse effects of earthquakes. The estimation of the impact from earthquakes considering the observed ground shaking from past events can be useful for the calibration of existing exposure and/or fragility and vulnerability models. This study describes a methodology to combine the publicly available information from the USGS ShakeMap system and the open‐source software OpenQuake engine for the assessment of damage and losses. This approach is employed to estimate the number of structural collapses considering the 2012 Magnitude 5.9 Emilia‐Romagna (Italy) earthquake and the aggregated economic loss because of the 2010 Magnitude 7.1 Darfield (New Zealand) event. Several techniques to calculate the ground shaking in the affected region considering the spatial and interperiod correlations in the intra‐event ground motion residuals are investigated and their influence in the resulting damage or loss estimates are evaluated.
Response to Maxam and Tamma's discussion (EQE‐18‐0306) to Kolay and Ricles's paper, “Development of a family of unconditionally stable explicit direct integration algorithms with controllable numerical energy dissipation”
Authors: Kolay Chinmoy , Ricles James M.
Published: February 2019

This paper presents the authors' response to the discussion by Dean J. Maxam and Kumar K. Tamma of the paper titled “Development of a family of unconditionally stable explicit direct integration algorithms with controllable numerical energy dissipation.”
Mixture design approach for the development of reduced fat lamb patties with carboxymethyl cellulose and inulin
Authors: Guedes‐Oliveira Juliana M. , Costa‐Lima Bruno R. C. , Oliveira Denize , Neto Adelino , Deliza Rosires , Conte‐Junior Carlos A. , Guimarães Carlos Frederico M.
Published: February 2019

Fat replacement by carboxymethyl cellulose (CMC) and inulin (IN) for the manufacture of low‐fat lamb patties was investigated utilizing mixture design. The effect of fat, CMC, and IN levels on texture, color, weight loss, patty diameter reduction, and sensory characteristics was investigated. The presence of CMC decreased hardness (p < 0.05). While CMC and IN also decreased springiness, cohesiveness, gumminess, and chewiness (p < 0.05), no effect on adhesiveness was observed (p > 0.05). CMC increased L* (lightness), a* (redness), and b* (yellowness) values in raw patties, whereas IN and fat contributed to a decrease on these parameters. Higher contents of CMC resulted in products with lower weight loss (p < 0.05) with no significative diameter reduction (p > 0.05). Nonetheless, higher levels of CMC affected the sensory acceptance resulting on products described as crumbly and with residual flavor by check‐all‐that‐apply questions. CMC and IN can be used as fat replacers in lamb patties; however, the content of each ingredient must be carefully considered. In this study, it was observed that contents of CMC higher than 1% (w/w) negatively affected the product, whereas IN levels were not capable to decrease weight loss and diameter reduction in lamb patties.
6‐Gingerol, an active pungent component of ginger, inhibits L‐type Ca2+ current, contractility, and Ca2+ transients in isolated rat ventricular myocytes
Authors: Han Xue , Zhang Yuanyuan , Liang Yingran , Zhang Jianping , Li Mengying , Zhao Zhifeng , Zhang Xuan , Xue Yurun , Zhang Ying , Xiao Jingkai , Chu Li
Published: February 2019

Ginger has been widely used as a flavor, food, and traditional medicine for centuries. 6‐Gingerol (6‐Gin) is the active components of ginger and offers some beneficial effects on cardiovascular diseases. Here, the effects of 6‐Gin on L‐type Ca2+ current (ICa‐L), contractility, and the Ca2+ transients of rat cardiomyocytes, were investigated via patch‐clamp technique and the Ion Optix system. The 6‐Gin decreased the ICa‐L of normal and ischemic ventricular myocytes by 58.17 ± 1.05% and 55.22 ± 1.34%, respectively. 6‐Gin decreased ICa‐L in a concentration‐dependent manner with a half‐maximal inhibitory concentration (IC50) of 31.25 μmol/L. At 300 μmol/L, 6‐Gin reduced the cell shortening by 48.87 ± 5.44% and the transients by 42.5 ± 9.79%. The results indicate that the molecular mechanisms underlying the cardio‐protective effects of 6‐Gin may because of a decreasing of intracellular Ca2+ via the inhibition of ICa‐L and contractility in rat cardiomyocytes.
Identification of a new inhibitor of KRAS‐PDEδ interaction targeting KRAS mutant nonsmall cell lung cancer
Authors: Leung Elaine Lai‐Han , Luo Lian Xiang , Li Ying , Liu Zhong‐Qiu , Li Lan Lan , Shi Dan Feng , Xie Ying , Huang Min , Lu Lin Lin , Duan Fu Gang , Huang Ju Min , Fan Xing Xing , Yuan Zhong Wen , Ding Jian , Yao Xiao Jun , Ward David C. , Liu Liang
Published: February 2019

Oncogenic KRAS is considered a promising target for anti‐cancer therapy. However, direct pharmacological strategies targeting KRAS‐driven cancers remained unavailable. The prenyl‐binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl‐binding pocket, impairing oncogenic KRAS signaling pathway. Here, we discovered a novel PDEδ inhibitor (E)‐N′‐((3‐(tert‐butyl)‐2‐hydroxy‐6,7,8,9‐tetrahydrodibenzo[b,dfuran‐1‐yl)methylene)‐2,4‐dihydroxybenzohydrazide(NHTD) by using a high‐throughput docking‐based virtual screening approach. In vitro and in vivo studies demonstrated that NHTD suppressed proliferation, induced apoptosis and inhibited oncogenic K‐RAS signaling pathways by disrupting KRAS‐PDEδ interaction in nonsmall cell lung cancer (NSCLC) harboring KRAS mutations. NHTD redistributed the localization of KRAS to endomembranes by targeting the prenyl‐binding pocket of PDEδ and exhibited the suppression of abnormal KRAS function. Importantly, NHTD prevented tumor growth in xenograft and KRAS mutant mouse model, which presents an effective strategy targeting KRAS‐driven cancer.
Contemporary Issues in Women's Health
Authors: Geary Michael , Guinto Valerie T. , Sosa Claudio G.
Published: February 2019

Uterus transplantation from a deceased donor

Does an awareness of fetal movements and a specific care package reduce the incidence of stillbirth? The AFFIRM stepped wedge, cluster‐randomized trial

Omega‐3 fatty acid supplementation during pregnancy reduces preterm birth
Modelling farmers' responses to irrigation water policies in Algeria: An economic assessment of volumetric irrigation prices and quotas in the Jijel–Taher irrigated perimeter
Authors: Oulmane Amine , Frija Aymen , Brabez Fatima
Published: February 2019

In Algeria, the management of water based on a strategy of supply and subsidies continues to be applied even as the resource becomes increasingly scarce. The demand for water in Algeria continues to grow, creating an imbalance between the available water resources and uses. In this context, the state has progressively implemented irrigation water management policies, including pricing, which aims to manage demand while reducing the water price subsidy. In this article we will study the effectiveness of some water management instruments implemented in the large irrigation perimeters and offer some perspectives to improve the management of the demand for irrigation water. To do so, we investigate the effect of different water pricing and irrigation quota scenarios on changing farmers' behaviour in terms of irrigation water demand. We developed a positive mathematical programming model based on farmers' surveys and typology in a public irrigated scheme (Jijel–Taher located in northern Algeria). Two types of scenarios were simulated, including: (i) increasing volumetric prices of irrigation water in the studied irrigated areas; (ii) decreasing water quota scenarios allocated to the farmers. As expected, results show that increasing water prices may lead to a decreasing demand for irrigation water. However, this decrease in water demand only became significant at very high prices. We also found that a price of 12.5 DZD m‾3 (about 0.11 US$ m‾3), corresponding to the government production cost of water, can easily be implemented in the study area without substantial effects on farmers' gross margin. Then, water pricing does not represent a water demand management tool, but rather a tool to finance management infrastructures. Simulations also show that decreasing water quotas may lead to a decrease of irrigated areas, change in cropping patterns, and to a significant loss of farmers' gross margins for quotas below 2600 m3 ha‾¹. © 2019 John Wiley & Sons, Ltd.
Genetic association of DNMT variants can play a critical role in defining the methylation patterns in autism
Authors: Alex Ann Mary , Saradalekshmi Korammannil R. , Shilen Neena , Suresh Poovathinal A. , Banerjee Moinak
Published: February 2019

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with impairments in social communication, restricted, repetitive and stereotyped behaviors. Both genetic and environmental factors are known to contribute toward pathophysiology of Autism. Environmental influences on gene expression can be mediated by methylation patterns which are established and maintained by DNA methyltransferases. Several studies in the past have investigated the role of global methylations in Autism. The present study is aimed to investigate the role of genetic variations in the DNA methyltransferase which might be critical in defining the threshold for environmental factors toward susceptibility to autism. Polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B, and DNMT3L were screened for association with ASD in 180 autistic patients and 260 healthy controls from a south Indian population. DNMT1 rs10418707 and rs10423341, and DNMT3A rs2289195 were found to be significantly associated at genotypic and allelic level with ASD. Functional prediction indicates that these SNPs have a role in transcriptional regulation and increased expression, indicating that hypermethylation might be induced by its genotype status. The study might reflect the role of genetics variants in DNMTs in defining the threshold of environmental impact in influencing the disease or phenotype variations in ASD. © 2019 IUBMB Life, 2019
Cytotoxicity profile of pristine graphene on brain microvascular endothelial cells
Authors: Rosas‐Hernandez Hector , Escudero‐Lourdes Claudia , Ramirez‐Lee Manuel A. , Cuevas Elvis , Lantz Susan M. , Imam Syed Z. , Majeed Waqar , Bourdo Shawn E. , Paule Merle G. , Biris Alexandru S. , Ali Syed F.
Published: February 2019

Graphene‐based nanomaterials hold the potential to be used in a wide variety of applications, including biomedical devices. Pristine graphene (PG) is an un‐functionalized, defect‐free type of graphene that could be used as a material for neural interfacing. However, the neurotoxic effects of PG, particularly to the blood‐brain barrier (BBB), have not been fully studied. The BBB separates the brain tissue from the circulating substances in the blood and is essential to maintain the brain homeostasis. The principal components of the BBB are brain microvascular endothelial cells (BMVECs), which maintain a protectively low permeability due to the expression of tight junction proteins. Here we analyzed the effects of PG on BMVECs in an in vitro model of the BBB. BMVECs were treated with PG at 0, 10, 50 and 100 μg/mL for 24 hours and viability and functional analyses of BBB integrity were performed. PG increased lactate dehydrogenase release at 50 and 100 μg/mL, suggesting the induction of necrosis. Surprisingly, 2,3,‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐5‐[(phenylamino)‐carbonyl]‐2H‐tetrazolium (XTT) conversion was increased at 10 and 50 μg/mL. In contrast, XTT conversion was decreased at 100 μg/mL, suggesting the induction of cell death. In addition, 100 μg/mL PG increased DNA fragmentation, suggesting induction of apoptosis. At the same time, 50 and 100 μg/mL of PG increased the endothelial permeability, which corresponded with a decrease in the expression of the tight junction protein occludin at 100 μg/mL. In conclusion, these results suggest that PG negatively affects the viability and function of the BBB endothelial cells in vitro.
Current state‐of‐the‐art and future perspectives of the three main modern implant‐dentistry concerns: Aesthetic requirements, mechanical properties, and peri‐implantitis prevention
Authors: López‐Píriz Roberto , Cabal Belén , Goyos‐Ball Lidia , Fernández Adolfo , Bartolomé José F. , Moya Jose S. , Torrecillas Ramón
Published: February 2019

The idea of permanent tooth replacement goes back to the year 2000 BC at least, when carved bamboo pegs were used to replace missing teeth in ancient China. The phenomenon of osseointegration, however, was not verified until the mid‐1960s, when Branemark discovered that titanium could integrate to bone. Since then, the osseointegration capacity of implants has been profoundly investigated and implants as such have evolved enormously in all possible aspects, from material selection and processing to specific surface engineering, among many others. This review article, in particular, focuses on dental implants and aims to introduce the main concerns involved in modern dentistry, concentrating especially on the importance of finding an effective way to prevent peri‐implantitis. In this sense, strategies such as shifting from metal to ceramic implant components and applying novel antimicrobial antibiotic‐free coatings seem to be taking the lead. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
Simple fabrication of inner chitosan‐coated alginate hollow microfiber with higher stability
Authors: Liu Hui , Wang Yaqing , Yu Yue , Chen Wenwen , Jiang Lei , Qin Jianhua
Published: February 2019

Sodium alginate (NaA) has been widely used as microfiber‐based scaffold material. However, Ca‐alginate microfiber might disintegrate in the physiological environment due to the loss of calcium ions, which will limit its long‐term application in tissue engineering. In this work, to enhance the stability of Ca‐alginate microfiber in the physiological environment, an inner chitosan coating was introduced to Ca‐alginate hollow microfiber by one step via a microfluidic device. A more stable composite microfiber with double cross‐linking layers was generated. The stability of the microfiber was studied in the PBS solution (pH 7.4) to identify the coating effect on the hollow structure. The results revealed that chitosan component bonded an NaA layer to form a stable polyelectrolyte complex membrane in the inner wall of the microfiber, which stabilized the hollow region even though the Ca‐alginate shell was disintegrated by PBS solution. In addition, the introduction of chitosan coating improved the inner environment of the low affinity of alginate to cell surfaces and facilitated the cell adhesion and culture in the microfiber. HepG2 cells in the microfibers displayed favorable cell viability and proliferation ability. We believe that this work will lead to the development of innovative methodologies and materials for both cell culture and tissue engineering application. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2527–2536, 2019.
Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial
Authors: Morse L R , Troy K L , Fang Y , Nguyen N , Battaglino R , Goldstein R F , Gupta R , Taylor J A
Published: February 2019

Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation‐ (FES‐) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES‐rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES‐rowing alone with FES‐rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV (p = 0.05 to 0.006), the CTI (p = 0.009), and the BR (p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing‐only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia (p = 0.05). A subgroup analysis of the rowing‐only arm showed that gains in the CSI at the tibial metaphysis varied in a dose‐dependent fashion based on the total amount of exercise performed (p = 0.009). These findings demonstrate that the osteogenic response to FES‐rowing is dose‐dependent. Combination therapy with ZA and FES‐row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Maternal Transient Receptor Potential Vanilloid 6 (Trpv6) Is Involved In Offspring Bone Development
Authors: Fecher-Trost Claudia , Lux Femke , Busch Kai-Markus , Raza Ahsan , Winter Manuel , Hielscher Franziska , Belkacemi Thabet , van der Eerden Bram , Boehm Ulrich , Freichel Marc , Weissgerber Petra
Published: February 2019

Embryonic growth and bone development depend on placental Ca2+ transport across the feto-maternal barrier to supply minerals to the fetus. The individual factors and cellular mechanisms that regulate placental Ca2+ transfer, however, are only beginning to emerge. We find that the Ca2+-selective transient receptor potential vanilloid 6 (TRPV6) channel is expressed in trophoblasts of the fetal labyrinth, in the yolk sac, and in the maternal part of the placenta. Lack of functional TRPV6 channels in the mother leads to a reduced Ca2+ content in both placenta and embryo. Ca2+ uptake in trophoblasts is impaired in the absence of Trpv6. Trpv6-deficient embryos are smaller, have a lower body weight, and shorter and less calcified femurs. The altered cortical bone microarchitecture persists in adulthood. We show that TRPV6's Ca2+-conducting property causes this embryonic and bone phenotype. Our results show that TRPV6 is necessary for the Ca2+ uptake in trophoblasts and that TRPV6 deficiency in the placenta leads to reduced embryo growth, minor bone calcification, and impaired bone development. © 2019 American Society for Bone and Mineral Research.
A comprehensive analysis of WGCNA and serum metabolomics manifests the lung cancer‐associated disordered glucose metabolism
Authors: Ding Mingchao , Li Fang , Wang Bin , Chi Guoqing , Liu Hao
Published: February 2019

Lung cancer is a worldwide disease and highly heterogeneous at a molecular level. In this study, we both performed the pathway enrichment analysis and the transcriptome‐based weighted gene coexpression network analysis (WGCNA) so as to find the critical pathways involved in lung cancer. Our analysis results indicated that genes in viability modules (0 < Z‐summary < 2) selected by WGCNA were more reliable for identifying crucial pathways, while gene enrichment analysis provided a wide range of pathways with a little emphasis on target pathways for lung cancer. On the basis of genes, which were classified into various modules by WGCNA, we found a significant aberration of glucose metabolism in lung cancer cells, demonstrating that the glucose metabolism has been perturbed, especially the glycolysis pathway. Our study revealed that disordered glucose metabolism might be closely associated with the carcinogenesis of lung cancer based on the integrated analysis of WGCNA and metabolomics, which could be a potential therapeutic target for lung cancer.
Sirtuin 6 mitigated LPS‐induced human umbilical vein endothelial cells inflammatory responses through modulating nuclear factor erythroid 2‐related factor 2
Authors: Qin Yi , Cao Lirong , Hu Lili
Published: February 2019

Background

Nuclear factor erythroid 2‐related factor 2 (Nrf2) protects the lung from sepsis‐induced injury through activating Nrf2‐regulated multiple phase 2 detoxification genes, including NAD(P)H: quinine oxidoreductase‐1 (NQO1) and heme oxygenase‐1 (HO1). Based on the positive effect of Sirtuin 6 on Nrf2, we aim to explore the potential role of SIRT6 in the mechanism of sepsis‐induced acute lung injury (ALI).

Methods

Mouse models of sepsis were constructed by instilling intratracheal of lipopolysaccharide (LPS; 4 ml/kg). After 48‐hour treatment, lung tissues were collected to measure the degree of lung injury. The SIRT6, siSIRT6, and siNrf2 plasmids were cotransfected into various concentrations of LPS‐treated human umbilical vein endothelial cells (HUVECs; 0, 1, 5, 10, and 50 μg/ml) using Lipofectamine 2000. Tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 levels were determined by enzyme‐linked immunosorbent assay. Expression levels of SIRT6, Nrf2, NQO1, and HO1 was measured by quantitative polymerase chain reaction and Western blot analysis. Cell apoptosis was determined by flow cytometry.

Results

Lung tissues in the model group already had basic characteristics of ALI. Compared with the control model, TNF‐α and IL‐6 levels were much higher (P < 0.01), the levels of SIRT6, Nrf2, and Nrf2‐modulated detoxification factors were downregulated (P < 0.01). SIRT6 overexpression decreased the apoptosis below to 10% (P < 0.01), significantly increased the Nrf2 expression, effectively inhibited TNF‐α and IL‐6 releases, and enhanced NQO1 and HO1 levels (P < 0.01). siNrf2 abolished the protective effects of SIRT6 overexpression, including increasing apoptosis and inhibiting anti‐inflammatory and antioxidative genes expressions (P < 0.01).

Conclusions

Our study suggested SIRT6 positively regulated Nrf2 expression and activated Nrf2‐regulated anti‐inflammatory and antioxidative enzymes, which could effectively mitigate LPS‐induced HUVECs inflammatory responses. This might reflect the mechanism of ALI induced by sepsis.
Biological features and regulatory mechanisms of salt tolerance in plants
Authors: Li Jingrui , Liu Min
Published: February 2019

Halophytes play a vital role in saline agriculture because these plants are necessary to increase the food supply to meet the demands of the growing world population. In addition, the transfer of salt‐resistance genes from halophytes using genetic technologies has the potential to increase the salt tolerance of xerophytes. Characterization of some particularly promising halophyte model organisms has revealed the important new insights into the salt tolerance mechanisms used by plants. Numerous advances using these model systems have improved our understanding of salt tolerance regulation and salt tolerance‐associated changes in gene expression, and these mechanisms have important implications for saline agriculture. Recent findings provide a basis for future studies of salt tolerance in plants, as well as the development of improved strategies for saline agriculture to increase yields of food, feed, and fuel crops.
mHDFS‐HoF: A generalized multilevel homodesmotic fragment‐separation reaction based program for heat‐of‐formation calculation for acyclic hydrocarbons
Authors: Nguyen Hieu Thanh , Mai Tam Van‐Thanh , Huynh Lam Kim
Published: February 2019

Based on our modified classification of elemental species, a framework for automatic generation of multilevel Homodesmotic fragment‐separation (mHDFS) reactions for chemical species was proposed. Combined the mHDFS framework with a database of heat of formation (HoF) and the calculated electronic structure data for the elemental mHD species, the mHDFS‐HoF program was constructed in C/C++ language to calculate heat of formation for a species of interest on‐the‐fly. Using the electronic structure data calculated at CBS‐QB3 level of theory for the elemental mHD species, applications and robustness of the code were discussed with several acyclic hydrocarbon systems including neutral and radical species. On‐going work and extension to other systems were also discussed. The program and the supporting files can be freely downloaded at https://sites.google.com/view/mhdfs/. © 2019 Wiley Periodicals, Inc.
Regulation of P300 and HDAC1 on endoplasmic reticulum stress in isoniazid‐induced HL‐7702 hepatocyte injury
Authors: Li Jin‐Feng , Li Ying‐Shu , Zhang Yi‐Yang , Sun Shu‐Feng , Han Tie‐Sheng , Li Yu‐Hong , Feng Fu‐Min
Published: February 2019

P300 and HDAC1 can be involved in the development of various liver diseases by regulating gene transcription. Endoplasmic reticulum stress (ERS) is one of the main pathways of apoptosis and is activated during inflammatory responses, but the roles of P300 and HDAC1 in ERS in antituberculosis drug‐induced liver injury (ADLI) are not clear. This study confirms that isoniazid can change the states of P300 and HDAC1 in HL‐7702 hepatocyte metabolism and induce ERS, causing hepatocyte injury and apoptosis. When combined with C646, however, P300 can be reduced. HL‐7702 cells were flattened, and the cytoplasm became crinkled. To a certain extent, ERS was relieved, but hepatocytes suffered worse damage, and the rate of cell apoptosis markedly increased. When MS‐275 was applied, HDAC1 level was increased, cell fusion appeared, and fluorescence intensity of endoplasmic reticulum was weakened. In addition, ERS was aggravated, but liver injury was relieved, and the apoptosis rate significantly decreased. Therefore, alteration of P300 and HDAC1 status and ERS are involved in ADLI, and changes in P300 and HDAC1 can regulate ERS and then affect cell damage.
Current information on the association of Helicobacter pylori with autophagy and gastric cancer
Authors: Eslami Majid , Yousefi Bahman , kokhaei Parviz , arabkari Vahid , Ghasemian Abdolmajid
Published: February 2019

Helicobacter pylori (H. pylori) is a Gram‐negative bacterium and causative agent of gastric cancer. H. pylori induce defective autophagy or inhibit it by means of CagA and vacuolating cytotoxin A (VacA) toxins leading to the gastric cancer induction. Impaired or defective autophagy leads to the accumulation of cytotoxic materials, such as ROS and P62 that lead to increased mutations in the DNA, genome instability, and risk of cancer formation. H. pylori CagA may inhibit autophagy through the c‐Met‐PI3k/Akt‐mTOR signaling pathway. However, VacA induces autophagy by some signaling pathways. In the gastric epithelial cells, VacA is a necessary and sufficient factor for the creation of autophagy. While CagA is a negative regulator of this phenomenon, the elimination of this gene from H. pylori has increased autophagy and the production of inflammatory cytokines is reduced. In gastrointestinal cancers, some of the microRNAs (miRNAs) act as tumor suppressors and some other are oncogenes by regulating various genes expression. H. pylori can also modify autophagy through a mechanism that includes the function of miRNAs. In autophagy, oncogenic miRNAs inhibit activation of some tumor suppressor signaling pathways (e.g., ULK1 complex, Beclin‐1 function, and Atg4 messaging), whereas tumor suppressor miRNAs can block the activation of oncogenic signaling pathways. For instance, Beclin‐1 is negatively regulated by miRNA‐376b (oncogenic miRNA) and miRNA‐30a (tumor suppressor miRNA). Similarly, Atg4 by miRNA‐376b (oncogenic miRNA) and miRNA‐101 (tumor suppressor miRNA). So, this apparent paradox can be explained as that both Beclin‐1 and Atg4 play different roles in a particular cell or tissue.
Is it true that gut microbiota is considered as panacea in cancer therapy?
Authors: Salek Farrokhi Amir , Darabi Narges , Yousefi Bahman , Askandar Rafee Habib , Shariati Mansoreh , Eslami Majid
Published: February 2019

Recent studies demonstrated that a combination of the gut microbiome has the vital effect on the efficacy of anticancer immune therapies. Regulatory effects of microbiota have been shown in different types of cancer therapies such as chemotherapy and immunotherapy. Immune‐checkpoint‐blocked therapies are the recent efficient cancer immunotherapy strategies. The target of immune‐checkpoint blocking is cytotoxic T lymphocyte protein‐4 (CTLA‐4) or blockade of programmed death‐1 (PD‐1) protein and its ligand programmed death ligand 1 (PD‐L1) that they have been considered as cancer immunotherapy in recent years. In the latest studies, it have been demonstrated that several gut bacteria such as Akkermansia muciniphila,
Bifidobacterium spp.,
Faecalibacterium spp., and
Bacteroides fragilis have the regulatory effects on PD‐1, PD‐L1, and CTLA‐4 blocked anticancer therapy outcome.
Combinatorial effect of blueberry extracts and oxaliplatin in human colon cancer cells
Authors: Lin Yang , Li Bin , Zhao Jin , Wei Lulu , Wang Yuehua , Wang Mingyue , Dia Vermont P. , Meng Xianjun
Published: February 2019

The use of natural compounds to potentiate the effect of drugs and lower their adverse effects is an active area of research. The objective is to determine the effect of combined blueberry extracts (BE) and oxaliplatin (OX) in colon cancer cells. The results demonstrated that treatments of BE/OX showed inhibitory effects on HCT‐116 cell and nontoxic effect on CCD‐18Co normal colon cells. Flow cytometry analysis indicated that treatment with the BE, OX or in combination could induce G0/G1 cell cycle arrest, apoptosis, increase of reactive oxygen species, and induce loss of mitochondrial membrane potential in HCT‐116 cells. Furthermore, after treatments, the expression of inflammatory cytokines was decreased, cyclin D1 and CDK4 were decreased; caspases‐3 and 9 were activated; the Akt/Bad/Bcl‐2 pathway was modulated. Moreover, the combination treatment had a considerably higher growth inhibitory effect on human colon cancer HCT‐116 cells than that of BE or oxaliplatin alone. Our results showed that BE increased the anticolon cancer effect of OX making it an attractive strategy as adjuvant therapy to potentially reduce the adverse side effects associated with chemotherapeutic drugs.
A promising structural magnetic resonance imaging assessment in patients with preclinical cognitive decline and diabetes mellitus
Authors: Dong Yulan , Wang Qi , Yao Hailun , Xiao Yawen , Wei Jiaohong , Xie Peihan , Hu Jun , Chen Wen , Tang Yan , Zhou Hong , Liu Jincai
Published: February 2019

Subjective cognitive decline (SCD) is frequently reported in diabetic patients. Diabetes mellitus (DM) is associated with changes in the microstructure of the brain arise in diabetic patients, including changes in gray matter volume (GMV). However, the underlying mechanisms of changes in GMV in DM patients with cognitive impairment remain uncertain. Here, we present an overview of amyloid‐β‐dependent cognitive impairment in DM patients with SCD. Moreover, we review the evolving insights from studies on the GMV changes in GMV and cognitive dysfunction to which provide the mechanisms of cognitive impairment in T2DM. Ultimately, the novel structural magnetic resonance imaging (MRI) protocol was used for detecting neuroimaging biomarkers that can predict the clinical outcomes in diabetic patients with SCD. A reliable MRI protocol would be helpful to detect neurobiomarkers, and to understand the pathological mechanisms of preclinical cognitive impairment in diabetic patients.
Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity
Authors: Ziolkowski Susan L. , Long Jin , Baker Joshua F. , Chertow Glenn M. , Leonard Mary B.
Published: February 2019

Background

Conventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to determine the associations of sarcopenia and relative sarcopenia with mortality independent of co‐morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations.

Methods

Dual energy X‐ray absorptiometry‐derived appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2) were assessed in 14 850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow‐up through 2011. Sarcopenia was defined using sex‐specific and race/ethnicity‐specific standard deviation scores compared with young adults (T‐scores) as an ALMI T‐score < −2 and relative sarcopenia as fat‐adjusted ALMI (ALMIFMI) T‐score < −2. Glomerular filtration rate (GFR) was estimated using creatinine‐based (eGFRCr) and cystatin C‐based (eGFRCys) regression equations.

Results

Three (3.0) per cent of National Health and Nutrition Examination Survey participants met criteria for sarcopenia and 8.7% met criteria for relative sarcopenia. Sarcopenia and relative sarcopenia were independently associated with mortality (HR sarcopenia 2.20, 95% CI 1.69 to 2.86; HR relative sarcopenia 1.60, 95% CI 1.31 to 1.96). The corresponding population attributable risks were 5.2% (95% CI 3.4% to 6.4%) and 8.4% (95% CI 4.8% to 11.2%), respectively. Relative sarcopenia remained significantly associated with mortality (HR 1.32, 95% CI 1.08 to 1.61) when limited to the subset who did not meet the criteria for sarcopenia. The risk of mortality associated with relative sarcopenia was attenuated among persons with higher FMI (P for interaction <0.01) and was not affected by CKD status for either sarcopenia or relative sarcopenia.

Conclusions

Sarcopenia and relative sarcopenia are significantly associated with mortality regardless of CKD status. Relative sarcopenia is nearly three‐fold more prevalent amplifying its associated mortality risk at the population level. The association between relative sarcopenia and mortality is attenuated in persons with higher FMI.
Design and numerical simulation of a novel microfluidic electroosmotic micromixer with three electrode pairs
Authors: Chen Xueye , Wu Zeyang
Published: February 2019

BACKGROUND

Miniaturization of experimental instruments in the field of biochemistry and medicine has become more and more common. A major trend in microfluidic technology is the miniaturization of experimental instruments. The relatively simple design and fabrication of active micromixers has attracted more and more attention.

RESULTS

In this paper, we design and simulate a novel electroosmotic micromixer that uses microelectrodes located in microchannel walls. The study first compares the mixing effect of the micromixer without and with electrodes, and then investigates the effects of the number of electrode pairs, the value of the alternating voltage and the AC frequency on the mixing performance.

CONCLUSION

When the electroosmotic micromixer has three electrode pairs at alternating voltage of 10 V and alternating frequency of 16 Hz, the best mixing efficiency can reach 98.2%. We call this micromixer TEEM (three electrode electroosmotic micromixer). At the same flow velocity, the mixing efficiency of TEEM is 30% higher than the electrodeless micromixer. This paper provides an effective theoretical support for the design of active electroosmotic micromixers, and provides a potential application value for further research and manufacture of electroosmotic micromixers used in biomedicine. © 2019 Society of Chemical Industry
Acute cardiac effects of high dose steroid treatment: A speckle tracking echocardiography study
Authors: Aksakal Emrah , Simsek Ziya , Aksu Uğur , Birdal Oguzhan , Ateş Esma Selva , Kalkan Kamuran , Gulcu Oktay , Demirelli Selami , Aksakal Enbiya , Tas Hakan
Published: February 2019

Purpose

High‐dose steroid therapy (HDST) has frequent side‐effects that appear at its cessation and depend on its dose. However, there is a lack of studies about the acute effects of HDST on cardiac function in adult patients.

Methods

We included in this study 30 patients who underwent HDST (intravenously at doses ranging from 250 to 1000 mg) and 30 healthy control subjects with similar demographic and clinical characteristics, between September and December 2016. Echocardiographic measurements were made before and during the first 3 hours after the end of treatment, and results were compared between patients and controls.

Results

There was no difference in baseline biochemical and echocardiographic characteristics between the patient and control groups. While left ventricular global longitudinal strain (LVGLS) and strain rate E were higher after treatment, no significant change was observed in conventional echocardiographic variables.

Conclusions

LVGLS, but not conventional echocardiographic variables, showed an increase in cardiac systolic function at the acute phase of HDST.
Creating cell and animal models of human disease by genome editing using CRISPR/Cas9
Authors: Zarei Ali , Razban Vahid , Hosseini Seyed Ebrahim , Tabei Seyed Mohammad Bagher
Published: February 2019

A set of unique sequences in bacterial genomes, responsible for protecting bacteria against bacteriophages, has recently been used for the genetic manipulation of specific points in the genome. These systems consist of one RNA component and one enzyme component, known as CRISPR (“clustered regularly interspaced short palindromic repeats”) and Cas9, respectively. The present review focuses on the applications of CRISPR/Cas9 technology in the development of cellular and animal models of human disease. Making a desired genetic alteration depends on the design of RNA molecules that guide endonucleases to a favorable genomic location. With the discovery of CRISPR/Cas9 technology, researchers are able to achieve higher levels of accuracy because of its advantages over alternative methods for editing genome, including a simple design, a high targeting efficiency and the ability to create simultaneous alterations in multiple sequences. These factors allow the researchers to apply this technology to creating cellular and animal models of human diseases by knock‐in, knock‐out and Indel mutation strategies, such as for Huntington's disease, cardiovascular disorders and cancers. Optimized CRISPR/Cas9 technology will facilitate access to valuable novel cellular and animal genetic models with respect to the development of innovative drug discovery and gene therapy.