bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a simple, inexpensive, in situ sampler for measuring time‐weighted average concentrations of suspended sediment in rivers and streams
Authors: Doriean Nicholas J.C. , Teasdale Peter R. , Welsh David T. , Brooks Andrew P. , Bennett William W. 
Published: November 2018

AbstractThe accurate measurement of suspended sediment (<200 μm) in aquatic environments is essential to understand and effectively manage changes to sediment, nutrient, and contaminant concentrations on both temporal and spatial scales. Commonly used sampling techniques for suspended sediment either lack the ability to accurately measure sediment concentration (e.g., passive sediment samplers) or are too expensive to deploy in sufficient number to provide landscape‐scale information (e.g., automated discrete samplers). Here, we evaluate a time‐integrated suspended sediment sampling technique, the pumped active suspended sediment (PASS) sampler, which collects a sample that can be used for the accurate measurement of time‐weighted average (TWA) suspended sediment concentration and sediment particle size distribution. The sampler was evaluated against an established passive time‐integrated suspended sediment sampling technique (i.e., Phillips sampler) and the standard discrete sampling method (i.e., manual discrete sampling). The PASS sampler collected a sample representative of TWA suspended sediment concentration and particle size distribution of a control sediment under laboratory conditions. Field application of the PASS sampler showed that it collected a representative TWA suspended sediment concentration and particle size distribution during high flow events in an urban stream. The particle size distribution of sediment collected by the PASS and Phillips samplers were comparable and the TWA suspended sediment concentration of the samples collected using the PASS and discrete sampling techniques agreed well, differing by only 4% and 6% for two different high flow events. We should note that the current configuration of the PASS sampler does not provide a flow‐weighted measurement and, therefore, is not suitable for the determination of sediment loads. The PASS sampler is a simple, inexpensive, and robust in situ sampling technique for the accurate measurement of TWA suspended sediment concentration and particle size distribution.
Interannual variability in glacier contribution to runoff from a high‐elevation Andean catchment: understanding the role of debris cover in glacier hydrology
Authors: Burger Flavia , Ayala Alvaro , Farias David , Shaw Thomas E. , MacDonell Shelley , Brock Ben , McPhee James , Pellicciotti Francesca 
Published: November 2018

AbstractWe present a field‐data rich modelling analysis to reconstruct the climatic forcing, glacier response, and runoff generation from a high‐elevation catchment in central Chile over the period 2000–2015 to provide insights into the differing contributions of debris‐covered and debris‐free glaciers under current and future changing climatic conditions. Model simulations with the physically based glacio‐hydrological model TOPKAPI‐ETH reveal a period of neutral or slightly positive mass balance between 2000 and 2010, followed by a transition to increasingly large annual mass losses, associated with a recent mega drought. Mass losses commence earlier, and are more severe, for a heavily debris‐covered glacier, most likely due to its strong dependence on snow avalanche accumulation, which has declined in recent years. Catchment runoff shows a marked decreasing trend over the study period, but with high interannual variability directly linked to winter snow accumulation, and high contribution from ice melt in dry periods and drought conditions. The study demonstrates the importance of incorporating local‐scale processes such as snow avalanche accumulation and spatially variable debris thickness, in understanding the responses of different glacier types to climate change. We highlight the increased dependency of runoff from high Andean catchments on the diminishing resource of glacier ice during dry years.
Measuring the natural rate of interest: A note on transitory shocks
Authors: Lewis Kurt F. , Vazquez‐Grande Francisco 
Published: November 2018

SummaryWe present evidence that the natural rate of interest is buffeted by both permanent and transitory shocks. We establish this result by estimating a benchmark model with Bayesian methods and loose priors on the unobserved drivers of the natural rate. When subject to transitory shocks, the median estimate for the US economy is more procyclical, displays a less marked secular decline, and is therefore higher following the Great Recession than most estimates in the literature.
SP1, MYC, CTNNB1, CREB1, JUN genes as potential therapy targets for neuropathic pain of brain
Authors: Yan Xue‐Tao , Xu Yong , Cheng Xiao‐Li , He Xiang‐Hu , Wang Yu , Zheng Wen‐Zhong , Zhao Ying , Chen Hu , Wang Yan‐Lin 
Published: November 2018

AbstractNeuropathic pain (NP) may cause serious brain diseases, but the genes associated with the metabolic pathway and transcript factors of NP remain unclear. This study is aimed to identify the therapy target genes for NP and to investigate the metabolic pathways and transcript factors associated with NP. The differentially expressed genes of three brain tissues (nucleus accumbens, periaqueductal gray, and prefrontal cortex) dealt with NP stimulation were analyzed. Besides, The Database for Annotation, Visualization, and Integrated Discovery and Tfacts datasets were used in the analysis of the genes related to the metabolic pathway and transcript factors of the brain. Eight genes were found to coexpress in all three tissues. A functional enrichment analysis showed that the upregulated genes were mostly enriched in pathways as inflammatory response, calcium‐mediated signaling, cytokine‐cytokine receptor interaction, and extracellular matrix (ECM)‐receptor interaction, whereas the downregulated genes were mostly enriched in pathways as phospholipid metabolic processes, positive regulation of protein kinase B signaling, and metabolism of xenobiotics by cytochrome P450. Finally, 135 and 98 transcript factors genes were upregulated and downregulated, among which SP1, MYC, CTNNB1, CREB1, JUN were identified as the most critical genes because the number of up‐ and downregulated gene ranked at the top. In conclusion, the pathways of immune response and cytokine‐cytokine receptor interaction were determined as the main metabolic pathways of NP affecting the brain, and SP1, MYC, CTNNB1, CREB1, JUN genes were recognized as the most enriched genes in this process, which may provide evidence for the diagnosis and treatment research of neuropathic pain.
Antibody–drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes
Authors: Abdollahpour‐Alitappeh Meghdad , Lotfinia Majid , Gharibi Tohid , Mardaneh Jalal , Farhadihosseinabadi Behrouz , Larki Pegah , Faghfourian Babak , Sepehr Koushan Sineh , Abbaszadeh‐Goudarzi Kazem , Abbaszadeh‐Goudarzi Ghasem , Johari Behrooz , Zali Mohammad Reza , Bagheri Nader 
Published: November 2018

AbstractTargeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody–drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more‐stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.
Molecular interaction of NFκB and NICD in monocyte–macrophage differentiation is a target for intervention in atherosclerosis
Authors: Binesh Ambika , Devaraj Sivasithamparam Niranjali , Halagowder Devaraj 
Published: November 2018

AbstractThe activation of two transcription factors, NFκB and NICD (notch intracellular domain), plays a crucial role in different stages of atherosclerotic disease progression, from early endothelial activation by modified lipids like oxidized low‐density lipoprotein (oxyLDL) to the imminent rupture of the atherosclerotic plaque. Inflammatory mediators and the notch pathway proteins were upregulated in atherogenic diet‐induced rats and the same was confirmed by the differentiation of monocyte to macrophage on exposure to oxyLDL. The inflammatory transcription factor NFκB and the notch signaling transcription factor NICD were analysed for their molecular interaction in monocyte to macrophage differentiation. Inhibition of NFκB by dexamethasone in monocyte to macrophage differentiation resulted in a concomitant downregulation of NICD, whereas inhibition of NICD by N‐(N‐[3, 5‐difluorophenacetyl])‐l‐alanyl)‐S‐phenylglycine t‐butyl ester (DAPT), a γ–secretase inhibitor, did not significantly influence the expression of NFκB, but downregulated macrophage differentiation. These findings revealed that NFκB inhibition using dexamethasone regulated NICD, which turned down macrophage differentiation. Thus, inhibition of both NFκB–NICD is a potential target for intervention in atherosclerosis.
Central adiponectin induces trabecular bone mass partly through epigenetic downregulation of cannabinoid receptor CB1
Authors: Jiang Hua , Wu Yuwei , Valverde Paloma , Murray Dana , Tang Jin , Yao Qi , Han Qianqian , Zhang Jin , Zhang Lan , Sui Lei , Tang Yin , Tu Qisheng , Chen Jake 
Published: November 2018

AbstractCentral adiponectin (APN) in either the globular (gAPN) or full‐length forms decreases sympathetic tone and increases trabecular bone mass in mice through the hypothalamus. It is known that cannabinoid type‐1 (CB1) receptors are expressed in the hypothalamic ventromedial nucleus and participate in energy metabolism by controlling sympathetic activity. However, whether central APN could influence endocannabinoid signaling through CB1 receptor to regulate bone metabolism has not been characterized. Here we demonstrate that gAPN downregulated CB1 expression in embryonic mouse hypothalamus N1 cells in vitro. gAPN intracerebroventricular (icv) infusions also decreased hypothalamic CB1 expression and bone formation parameters in APN‐knockout (APN‐KO) and wild‐type mice. Most importantly, mice pretreated with icv infusions with the CB1 receptor agonist arachidonyl‐2′‐chloroethylamine or antagonist rimonabant attenuated or enhanced respectively central APN induction of bone formation. We then investigated whether epigenetic signaling mechanisms were involved in the downregulation of hypothalamic CB1 expression by gAPN. We found gAPN enhanced expression levels of various histone deacetylases (HDACs), especially HDAC5. Furthermore, chromatin immunoprecipitation assays revealed HDAC5 bound to the transcriptional start site transcription start site 2 region of the CB1 promoter. In summary, our study identified a possible novel central APN‐HDAC5‐CB1 signaling mechanism that promotes peripheral bone formation through epigenetic regulation of hypothalamic CB1 expression.
Human breast cancer decellularized scaffolds promote epithelial‐to‐mesenchymal transitions and stemness of breast cancer cells in vitro
Authors: Liu Gang , Wang Biao , Li Shubin , Jin Qin , Dai Yanfeng 
Published: November 2018

AbstractBreast cancer, with unsatisfactory survival rates, is the leading cause of cancer‐related death in women worldwide. Recent advances in the genetic basis of breast cancer have benefitted the development of gene‐based medicines and therapies. Tissue engineering technologies, including tissue decellularizations and reconstructions, are potential therapeutic alternatives for cancer research and tissue regeneration. In our study, human breast cancer biopsies were decellularized by a detergent technique, with sodium lauryl ether sulfate (SLES) solution, for the first time. And the decellularization process was optimized to maximally maintain tissue microarchitectures and extracellular matrix (ECM) components with minimal DNA compounds preserved. Histology analysis and DNA quantification results confirmed the decellularization effect with maximal genetic compounds removal. Quantification, immunofluorescence, and histology analyses demonstrated better preservation of ECM components in 0.5% SLES‐treated scaffolds. Scaffolds seeded with MCF‐7 cells demonstrated the process of cell recellularization in vitro, with increased cell migration, proliferation, and epithelial‐to‐mesenchymal transition (EMT) process. When treated with 5‐fluorouracil, the expressions of stem cell markers, including Oct4, Sox2, and CD49F, were maximally maintained in the recellularized scaffold with decreased apoptosis rates compared with monolayer cells. These results showed that the decellularized breast scaffold model with SLES treatments would help to simulate the pathogenesis of breast cancer in vitro. And we hope that this model could further accelerate the development of effective therapies for breast cancer and benefit drug screenings.
Inhibition of miR‐124 improves neonatal necrotizing enterocolitis via an MYPT1 and TLR9 signal regulation mechanism
Authors: Yin Yiyu , Qin Zhenfang , Xu Xiaobing , Liu Xu , Zou Huaxin , Wu Xiaole , Cao Junhua 
Published: November 2018

AbstractBackgroundsNecrotizing enterocolitis (NEC) was one of the main causes of morbidity and mortality in neonates. Our objective was to detect the mechanism of miR‐124 in small bowel tissues of NEC.MethodsHematoxylin and eosin (H&E) staining was used to detect the repair of the damaged tissues in rat NEC model. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to evaluate the cell apoptosis level in intestinal tissue. Reverse transcription polymerase chain reaction (RT‐PCR) was used to detect the messenger RNA (mRNA) expression level of miR‐124, Rho‐associated coiled‐coil‐containing protein kinase 1 (ROCK1), myosin phosphatase target subunit 1 (MYPT1), and Toll‐like receptor 9 (TLR9) in NEC tissues and IEC‐6 cells. Luciferase reporter assay was used to verify whether ROCK1 is a direct target of miR‐124.ResultsmiR‐124 was overexpressed in the NEC tissues, while ROCK1 and MYPT1 was downregulated in the NEC tissues. Inhibition of miR‐124, suppressed the intestinal cell apoptosis and promoted the expression of ROCK1 and MYPT1. What is more, overexpression of miR‐124 could inhibit the expression of ROCK1, TLR9, and MYPT1. Luciferase assay confirmed that miR‐124 can regulate the transcriptional activity of ROCK1 through binding its 3′‐UTR region.ConclusionmiR‐124 was a promoter of NEC, which promotes the intestine cell apoptosis and inflammatory cell infiltration through the inhibition of TLR9 expression by targeting ROCK1.
Cell fate regulation by reticulon‐4 in human prostate cancers
Authors: Zhao Hu , Su Weipeng , Zhu Changyan , Zeng Tengyue , Yang Shunliang , Wu Weizhen , Wang Dong 
Published: November 2018

AbstractReticulon‐4 (RTN4), a reticulon family protein localized in the endoplasmic reticulum, is reported to be involved in multiple physiological processes like neuroendocrine secretion and membrane trafficking in neuroendocrine cells. Previous studies have presented a great potential of RTN4 for the treatment of autoimmune‐mediated demyelinating diseases and spinal cord injury regeneration. While interaction with Bcl‐2 and Bcl‐2‐like family in apoptosis modulation implicated its possible role in various human cancers. However, the investigation of this gene in prostate cancer is mainly ignored. Here in our current study, we focused on its role in prostate cancer and found that RTN4 DNA copy numbers were higher in prostate cancer than normal prostate gland while its RNA and protein expressions were relatively lower. Chromosomal neighbor gene EML6 had similar expression patterns with RTN4 in prostate cancer tissues and cell lines, and further research found that they could be both targeted by miR‐148a‐3p. Lentivirus‐mediated RTN4 overexpression potently inhibited DU145 and LNCaP cells proliferation. Cell cycle was blocked in G2/M phase and significant cell senescence was observed in RTN4 overexpressed prostate cancer cells. Finally, interaction networks in the normal prostate gland and cancer tissues further revealed that RTN4 maybe phosphorylated by MAPKAPK2 and FYN at tyrosine 591 and serine 107, respectively. All these results implied that RTN4 might somehow participate in prostate tumor progression, and this elicits possibility to develop or identify selective agents targeting RTN4 for prostate cancer therapy.
Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts
Authors: Jing Ying , Li Li , Li Yuan‐Yuan , Ouyang Ying‐Chun , Sun Qing‐Yuan , Zhang Cui‐Lian , Li Rong 
Published: November 2018

AbstractIt has been shown recently that there is premature mitochondria biosynthesis in blastocysts from older women whose egg or embryo quality is poor and that aneuploid blastocysts also have a high number of mitochondrial DNA (mtDNA) copies. Whether nondiploidy/aneuploidy or reduced egg or embryo quality causes premature mitochondrial biosynthesis is not known. This study constructed haploid, diploid, triploid, and tetraploid blastocysts by parthenogenetic activation, intracytoplasmic sperm injection with one or two sperm heads, blastomere electrofusion, respectively, and generated reduced cytoplasm quality embryos from diabetic mouse and in vitro fertilization of aged oocytes, and examined whether nondiploidy or reduced cytoplasm quality causes premature mitochondrial biosynthesis. MtDNA numbers of each blastocyst from different models were tested by absolute quantitative real‐time polymerase chain reaction. It was found that mtDNA content in preimplantation embryos was not associated with their chromosome ploidy, while mtDNA copy numbers in embryos with suboptimal quality were increased. Therefore, it might be the reduced cytoplasmic quality, and not chromosome nondiploidy, that causes premature mitochondria biosynthesis in blastocysts.
Cholinergic activity regulates the secretome of epicardial adipose tissue: Association with atrial fibrillation
Authors: Couselo‐Seijas Marinela , López‐Canoa Jose N. , Agra‐Bermejo Rosa M. , Díaz‐Rodriguez Esther , Fernandez Angel L. , Martinez‐Cereijo Jose M. , Durán‐Muñoz Dario , Bravo Susana B. , Velo Alba , González‐Melchor Laila , Fernández‐López Xesus A. , Martínez‐Sande Jose L. , García‐Seara Javier , González‐Juanatey Jose R. , Rodriguez‐Mañero Moises , Eiras Sonia 
Published: November 2018

AbstractBotulinum toxin injection on epicardial fat, which inhibits acetylcholine (ACh) release, reduced the presence of atrial fibrillation (AF) in patients after heart surgery. Thus, we wanted to study the profile of the released proteins of epicardial adipose tissue (EAT) under cholinergic activity (ACh treatment) and their value as AF predictors. Biopsies, explants, or primary cultures were obtained from the EAT of 85 patients that underwent open heart surgery. The quantification of muscarinic receptors (mAChR) by real‐time polymerase chain reaction or western blot showed their expression in EAT. Moreover, mAChR Type 3 was upregulated after adipogenesis induction (p < 0.05). Cholinergic fibers in EAT were detected by vesicular ACh transporter levels and/or acetylcholinesterase activity. ACh treatment modified the released proteins by EAT, which were identified by nano‐high‐performance liquid chromatography and TripleTOF analysis. These differentially released proteins were involved in cell structure, inflammation, or detoxification. After testing the plasma levels of alpha‐defensin 3 (inflammation‐involved protein) of patients who underwent open heart surgery (
n = 24), we observed differential levels between the patients who developed or did not develop postsurgery AF (1.58 ± 1.61 ng/ml vs. 6.2 ± 5.6 ng/ml;
p < 0.005). The cholinergic activity on EAT might suggest a new mechanism for studying the interplay among EAT, autonomic nervous system dysfunction, and AF.
Effects of nebulized N­‐acetylcystein on the expression of HMGB1 and RAGE in rats with hyperoxia‐­induced lung injury
Authors: Qiao Junying , Chen Lixia , Huang Xianjie , Guo Feifei 
Published: November 2018

AbstractObjectiveTo investigate the role of high mobility group box 1 (HMGB1) and receptor for advanced glycation end product (RAGE) in the lungs of hyperoxia‐induced rats and the effect of N‐­acetlycystein (NAC).MethodsA model of hyperoxic lung injury was established, rats in the NAC intervention, and control, hyperoxia group were given nebulized NAC aerosol, nebulized same volume of saline once a day for 7 consecutive days, respectively. Wet/dry (
W/
D) ratio of the lungs was determined to evaluate the edema of the lung tissues. Conventional hematoxylin–eosin (HE) staining was used to observe the pathological changes of lung tissues. Immunohistochemical staining was used to investigate the expression of HMGB1 and RAGE in the lung tissues. Quantitative reverse‐transcription polymerase chain reaction and western blot analysis were used to measured the changes in the messenger RNA (mRNA) and protein expression of HMGB1 and RAGE, respectively.ResultsWeight gain of the rats in the hyperoxia group was significantly slower than that in the control group and intervention group (p < 0.05). HE staining results showed lung tissues in the hyperoxia group were severely damaged compared with control group. W/D ratio in hyperoxia group was significantly higher than that in control group and intervention group (p < 0.05). Protein and mRNA expression of HMGB1 and RAGE in the hyperoxia group were significantly higher than control group and intervention group (p < 0.05).ConclusionHMGB1 and RAGE were involved in the pathogenesis of hyperoxia‐induced lung injury, inhalation of NAC might alleviate hyperoxia‐induced lung injury by regulating the expression of HMGB1 and RAGE.
Preparation of adriamycin gelatin microsphere‐loaded decellularized periosteum that is cytotoxic to human osteosarcoma cells
Authors: Chen Chuan , Dong Jianghui , Chen Hong , Wang Xin , Mei Jin , Wang Liping , Xian Cory J 
Published: November 2018

AbstractThe purpose of this study was to develop a novel approach to treat bone osteosarcoma using a multipurpose scaffold aiming for local drug delivery. The slowly releasing microspheres was designed to deliver the chemotherapy drug adriamycin (ADM) and a decellularized (D) periosteum scaffold (which is known to be able to promote bone regeneration) was used to carry these microspheres. D‐periosteum was obtained by physical and chemical decellularization. Histological results showed that the cellular components were effectively removed. The D‐periosteum showed an excellent cytocompatibility and the ability to promote adhesion and growth of fibroblasts. Two kinds of slowly releasing microspheres, adriamycin gelatin microspheres (ADM‐GMS) and adriamycin poly (dl‐lactide‐co‐glycolide) gelatin microspheres (ADM‐PLGA‐GMS), were prepared and anchored to D‐periosteum, resulting in two types of drug‐releasing regenerative scaffolds. The effectiveness of these two scaffolds in killing human osteosarcoma cells was tested by evaluating cell viability overtime of the cancer cells cultured with the scaffolds. In summary, a gelatin/decellularized periosteum‐based biologic scaffold material was designed aiming for local delivery of chemotherapy drugs for osteosarcoma, with the results showing ability of the scaffolds in sustaining release of the cancer drug and in suppressing growth of the cancer cells in vitro.