bluuebunny/crossref_metadata_2025 huggingface dataset:
Deformation and rheological properties of Dashiqiao Formation of Liaohe Group in Hupiyu area, eastern Liaoning Province
Authors: Chang Ruihong , Liu Yongjiang , Li Weimin , Gu Daxiang
Published: January 2019

The study on deformation characters of the Liaohe Group, exposed in eastern Liaoning Province, NE China, provides a key constraint on the tectonic evolution of the Palaeoproterozoic Liao–Ji active belt in the eastern part of the North China Craton (NCC). In this paper, the deformation pattern and mechanism of the Dashiqiao Fm. from Liaohe Group in Hupiyu area have been systematically studied. The present results show that the structure of the investigated Dashiqiao Fm. exhibits a SW bedding‐parallel thrust shearing which is dominated by simple shearing. Simultaneously, S‐SL tectonites were formed under directional flattening. The deformed quartz grains show obvious dislocation slip which is mainly controlled by the low temperature system of the basal  slip system, while calcites mainly develop in low temperature with  twin slip. Based on microstructural analysis coupled with fabric features, we estimated that the strain rate is 10−12.78–10−8.32 s−1 under the deformation temperature of 350–400°C with a differential stress of 27.3–44.9 MPa. Our macrostructural–microstructural investigation together with previous researches indicates that the Liaohe Group suffered a bedding‐parallel sliding with top‐to‐outside away from the granite body in the core of Hupiyu anticline, corresponding to the uplift of the Hupiyu granite in the early extensional stage. Subsequently, the Hupiyu area suffered SW–NE compression which resulted in the overturn of the southern limb of the Hupiyu anticline and the top‐to‐SW thrusting.
Nitroselenation of carbon‐carbon triple bond by PhSeSePh and NO/O2 or NO2
Authors: Nishiyama Yutaka , Sumida Mari , Sonoda Noboru
Published: January 2019

When alkynes were treated with diphenyl diselenide under an atmosphere of nitric oxide and oxygen, nitroselenation of the carbon‐carbon triple bond proceeded with a high regioselectivity to give the corresponding 1‐nitro‐2‐phenylseleno alkenes. Similarly, the nitroselenation of alkynes proceeded by the reaction of the alkynes with nitrogen dioxide. The stirring of the 1,2‐bis(phenylseleno) alkenes under an atmosphere of nitric oxide and oxygen also gave the corresponding 1‐nitro‐2‐phenylseleno alkenes.
Ultrasonographic swallowing examination for early detection of neopharyngeal fistula after salvage total laryngectomy: A preliminary study
Authors: Ahn Dongbin , Lee Gil Joon , Sohn Jin Ho
Published: January 2019

Background

The current study investigated the feasibility of ultrasonographic swallowing examination (USSE) for the evaluation of neopharynx and early detection of neopharyngeal fistula after salvage total laryngectomy.

Methods

A prospective case series‐based study involving 16 patients who underwent salvage total laryngectomy was conducted. USSE was performed on postoperative days 5‐7, and oral diet initiation was determined based on the USSE results.

Results

Fistula of the neopharynx was detected in four patients (25%) via USSE, as was the specific site of the fistula. In these patients, oral diet was delayed and immediate interventions including ultrasound‐guided fluid aspiration and compression dressing were applied, and all fistulas were subsequently closed. In the remaining 12 patients with no neopharyngeal fistula on USSE, an oral diet was started immediately and no fistula occurred.

Conclusions

USSE is a promising method for neopharynx evaluation and early detection of neopharyngeal fistula after salvage total laryngectomy.
Inhibitors of the Bifunctional 2‐C‐Methyl‐d‐erythritol 4‐Phosphate Cytidylyl Transferase/2‐C‐Methyl‐d‐erythritol‐2,4‐cyclopyrophosphate Synthase (IspDF) ofHelicobacter pylori
Authors: Honold Annika , Lettl Clara , Schindele Franziska , Illarionov Boris , Haas Rainer , Witschel Matthias , Bacher Adelbert , Fischer Markus
Published: January 2019

A library of over 103 thousand compounds was screened for inhibitors of the IspD domain (2‐C‐methyl‐d‐erythritol 4‐phosphate cytidylyl transferase domain) of the bifunctional IspDF protein fromHelicobacter pyloriusing a photometric assay. Around 300 compounds showedIC50values below 100 μm, and three compounds hadIC50values below 1 μm. A few IspD inhibitors could also inhibit the IspF domain (2‐C‐Methyl‐d‐erythritol‐2,4‐cyclopyrophosphate synthase) of the IspDF protein. The most potent IspD inhibitors were tested as growth inhibitors ofH. pylori. Several compounds showed inhibition of bacterial growth withIC50in the single‐digit μmrange. The most potent growth inhibitor had anIC50value of 3.4 μm. The most potent growth inhibitor without measurable effect on eukaryotic cell viability had anIC50value of 7.2 μm.
Patient safety attitude in primary health care settings in Giza, Egypt: Cross‐sectional study
Authors: El Shafei Arwa Mohamed Hosney , Zayed Mouchira Amin
Published: January 2019

Background

Although there is increasing interest in patient safety, yet there is a general lack of awareness of the problem. This study aims to investigate patient safety attitudes among health care providers in primary health care (PHC) facilities in Egypt through employing the Safety Attitudes Questionnaire in order to explore the areas of deficiency and opportunities for improvement concerning patients' safety.

Methods

A cross‐sectional study was conducted in an urban PHC and one rural unit where 130 working team at the time of the study was interviewed with response rate of 63.7%, SPSS 18 was used for data analysis. Descriptive analyses, independent samples t tests, and/or analysis of variance (ANOVA) were performed to examine the relationship between patient's safety culture and independent variables, namely, profession, gender, or age groups.

Results

Highest positivity percentage was found for job satisfaction dimension (23%), while it was the least for the ambulatory care (2.3%). Participants belonging to age group older than or equal to 50 scored statistically significant mean values in both job satisfaction and working conditions dimensions (P = 0.03 and 0.02, respectively). Health care managers scored statistically significant mean in the ambulatory care dimension 68.1 ± 15.3, (P = 0.03).

Conclusion

Managers had more positive attitudes regarding patient safety issues in the practices they are responsible for, compared with the employees. This could be an opportunity to enhance safety attitudes within PHC centers and gain their commitment to guarantee safer and higher quality patient care.
Engaging customer care employees in internal collaborative crowdsourcing: Managing the inherent tensions and associated challenges
Authors: Malhotra Arvind , Majchrzak Ann , Bonfield William , Myers Steve
Published: January 2019

Customer care employees (CCEs) are an excellent source of ideas for new and enhanced services for customers. By serving many customers, CCEs have the ability to see patterns in unserved and underserved needs. By being inside rather than external to the firm, CCEs have the ability to offer suggestions that build on existing capabilities, which result in ideas that are more easily implementable. There is a long history of research and practice for soliciting suggestions from employees, but little of this work has described how CCEs can be organized into a temporary online crowd to cocreate innovative ideas. With the advent of crowdsourcing software platforms, online collaboration among geographically distributed CCEs is increasingly possible. We describe an action research study of Optum, a healthcare company that implemented a collaborative internal crowdsourcing initiative over a period of 18 months. The action research study led to the identification of three tensions and associated challenges. We outline eight HRM actions that were undertaken to mitigate the challenges of engaging CCEs in internal crowdsourcing efforts. Based on our findings, we lay out a general framework, implications, and future research directions for research and managerial actions when engaging CCEs in internal collaborative crowdsourcing.
Development of cold‐hot water dispenser with thermoelectric module systems
Authors: Hommalee Chootichai , Wiriyasart Songkran , Naphon Paisarn
Published: January 2019

In the present study, the results of a cold‐hot water dispenser with a thermoelectric module system (TMS) are presented. The cold‐hot water dispenser with thermoelectric module system consists of a cold water loop, a hot water loop, a coolant loop, and a thermoelectric module. The thermoelectric cooling and heating modules consist of four and two water blocks, nine and three thermoelectric plates, respectively. The cooling and heating capacities obtained from the cold‐hot water dispenser with TMS are compared with those from a conventional cold‐hot water dispenser with a compression refrigeration system (CRS). As compared with the conventional cold‐hot water dispenser with CRS, the cold‐hot water dispenser with TMS can be operated at the minimum cold water temperature of 10 to 13°C and the maximum hot water temperature of 65°C. The obtained results are expected provide guidelines to design cold‐hot water dispensers with TMS.
Sulfate variations as a natural tracer for conduit‐matrix interaction in a complex karst aquifer
Authors: Frank Simon , Goeppert Nadine , Ohmer Marc , Goldscheider Nico
Published: January 2019

Large areas of Europe, especially in the Alps, are covered by carbonate rocks, and karst springs are an important source for drinking water supply. Because of their high variability and heterogeneity, understanding the hydrogeological functioning is of particular importance for protection of karst aquifers. In this study, hydrogeochemical investigations characterized the water of a spring draining a complex carbonate‐gypsum karst system in the Alps. The reaction of the spring to a rainfall event was examined to identify the relevant hydrological processes controlling the hydrochemistry of the spring, and to understand water‐rock interactions and conduit–matrix exchange. A fast and marked reaction of discharge and electrical conductivity was observed. The main cations are Ca2+ and Mg2+, which showed a distinct decrease after the rainfall. Bicarbonate and sulfate were identified as major anions. Although HCO3− showed only minor fluctuations, SO42− decreased by 72% after the rain event. Comparisons of ion ratios show that both carbonate and gypsum rocks influence the water chemistry of the spring. The rainfall event caused a dilution effect, but dilution alone cannot explain the observed water chemistry. A conceptual model of the spring behaviour during low‐flow and high‐flow conditions, including conduit–matrix interaction, was developed, which can explain the observations. This study aims to give new insights into the highly dynamic exchange processes between karst conduits and the surrounding matrix, and the results demonstrated that (a) during low‐flow conditions, the spring is characterized by high sulfate content, but after rainfall events, the water chemistry is dominated by bicarbonate. These findings show the dependency of water chemistry from the lithology; (b) a change in water chemistry is associated with a significant shift from low‐flow to high‐flow conditions; (c) conduit–matrix exchange is an important factor as shown by the discharge–sulfate relationship and clearly influences the behaviour of the spring.
IL‐10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF‐κB/Notch1 pathway in non‐small cell lung cancer
Authors: Yang Li , Dong Ying , Li Yanjun , Wang Dong , Liu Shasha , Wang Dan , Gao Qun , Ji Shaofei , Chen Xinfeng , Lei Qingyang , Jiang Wenyi , Wang Liping , Zhang Bin , Yu Jane J. , Zhang Yi
Published: January 2019

Tumor‐associated macrophages (TAMs), key immune cells in the tumor microenvironment, are shown to be closely correlated with the progression of non‐small cell lung cancer (NSCLC). Cancer stem cells (CSCs) can contribute to NSCLC progression as well. We aimed to clarify whether TAMs promote the progression of NSCLC by mainly affecting the activities of CSCs. We found that TAM‐like cells promoted CSC‐like properties in NSCLC cells in vitro, which was mediated by TAM‐derived IL‐10. TAM‐derived IL‐10 promoted CSC‐like properties of NSCLC cells through JAK1/STAT1/NF‐κB/Notch1 signaling. Blockade of IL‐10/JAK1 signaling inhibited TAM‐mediated NSCLC tumor growth in vivo, and the TAM‐mediated expression of CSC‐related and mesenchymal‐related genes in NSCLC. Lastly, expression levels of these signaling molecules were significantly correlated with survival of NSCLC patients. Therefore, IL‐10/JAK1 signaling might be a potential therapeutic target for NSCLC treatment.
A Personal Perspective on Chemical Biology: Before the Beginning
Authors: Dervan Peter B.
Published: January 2019

This perspective represents a brief personal account of early days before “chemical biology” emerged as a field of inquiry. Imagine a time when oligomers of DNA could not be synthesized and the order of the TACG letters in DNA could not be sequenced. Even the high resolution structure of the DNA double helix was not yet determined. 1975 was a time when there was a deep chasm between chemistry and biology. Chemists with precise knowledge of all the atoms in natural product architectures looked with dismay at the imprecise messy world of biology. Water was to be avoided! My view was that the power of synthetic organic chemistry should be used to create function, synthesis with a purpose. Our organic group at Caltech would embrace molecular recognition of biologics in water as a frontier for chemistry. We dreamed of inventing small molecules that would control the activity of macromolecules such as DNA, proteins and carbohydrates in living cells. We chemists would sky dive into the messy world of biology.
Development of bifunctional oriented bioactive glass/poly(lactic acid) composite scaffolds to control osteoblast alignment and proliferation
Authors: Lee Sungho , Matsugaki Aira , Kasuga Toshihiro , Nakano Takayoshi
Published: January 2019

During the bone regeneration process, the anisotropic microstructure of bone tissue (bone quality) recovers much later than bone mass (bone quantity), resulting in severe mechanical dysfunction in the bone. Hence, restoration of bone microstructure in parallel with bone mass is necessary for ideal bone tissue regeneration; for this, development of advanced bifunctional biomaterials, which control both the quality and quantity in regenerated bone, is required. We developed novel oriented bioactive glass/poly(lactic acid) composite scaffolds by introducing an effective methodology for controlling cell alignment and proliferation, which play important roles for achieving bone anisotropy and bone mass, respectively. Our strategy is to manipulate the cell alignment and proliferation by the morphological control of the scaffolds in combination with controlled ion release from bioactive glasses. We quantitatively controlled the morphology of fibermats containing bioactive glasses by electrospinning, which successfully induced cell alignment along the fibermats. Also, the substitution of CaO in Bioglass®(45S5) with MgO and SrO improved osteoblast proliferation, indicating that dissolved Mg2+and Sr2+ions promoted cell adhesion and proliferation. Our results indicate that the fibermats developed in this work are candidates for the scaffolds to bone tissue regeneration that enable recovery of both bone quality and bone quantity. © 2019 The Authors.journal Of Biomedical Materials Research Part APublished By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1031–1041, 2019.
Synthesis and biological evaluation of novel indenopyrazole derivatives
Authors: Gezegen Hayreddin , Tutar Uğur , Hepokur Ceylan , Ceylan Mustafa
Published: January 2019

A series of novel indenopyrazole derivatives 2a‐j and
3a‐j were synthesized from the reaction of 1‐(4‐(hydroxy(1‐oxo‐1,3‐dihydro‐2
H‐inden‐2‐ylidene)methyl)phenyl)‐3‐phenylurea derivatives
1a‐j with hydrazine and phenylhydrazine, respectively. The obtained novel indenopyrazoles (
2a‐j and
3a‐j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay;
2a,
2b,
2d,
2h, and
3h were found to be the most active compounds. The compounds were also screened for antimicrobial activity, and all compounds showed moderate activity against used microorganisms.
Current status and future prospects of transforming growth factor‐β as a potential prognostic and therapeutic target in the treatment of breast cancer
Authors: Amerizadeh Forouzan , Bahrami Afsane , Khazaei Majid , Hesari AmirReza , Rezayi Majid , Talebian Sahar , Maftouh Mona , Moetamani‐Ahmadi Mehrdad , Seifi Sima , Shahidsales Soodabeh , Joudi‐Mashhad Mona , Ferns Gordon A. , Ghasemi Faezeh , Avan Amir
Published: January 2019

The transforming growth factor‐β (TGF‐β) signaling pathway is one of the important pathways involved in the cancer cell proliferation, invasion, migration, angiogenesis, apoptosis, as well as in metastasis by agitation or invasion of metastasis‐related factors, including matrix metalloproteinase (MMP), epithelial‐to‐mesenchymal transition (EMT), tumor microenvironment (TME), cancer stem cells (CSCs), and cell adhesion molecules (CAMs). These data suggest its potential value as a therapeutic object in the treatment of malignancies including breast cancer. Several pharmacological approaches have been established to suppress TGF‐β pathway; such as vaccines, small molecular inhibitors, antisense oligonucleotides, and monoclonal antibodies. Some of these are now approved by the US Food and Drug Administration for targeting the TGF‐β signaling pathway. This study attempts to summarize the current data about the functions of TGF‐β in cancer cells, and their probable application in the cancer therapy with a specific emphasis on recent preclinical and clinical research in the treatment of breast cancer and its prognostic value.
Epigenetic profiling and mRNA expression reveal candidate genes as biomarkers for colorectal cancer
Authors: Zhang Hui , Dong Shuchen , Feng Jifeng
Published: January 2019

Colorectal cancer (CRC) is characterized by DNA methylation, which is associated with genomic instability and tumor initiation. As an important epigenetic regulation, DNA methylation can be used as a potential therapeutic target for CRC. In our study, we downloaded DNA methylation profiles (GSE17648 and GSE29490) and RNA sequencing microarray data (GSE25070 and GSE32323) from the Gene Expression Omnibus (GEO) database. As a result, 14 aberrantly methylated differentially expressed genes (DEGs) were screened according to the different criteria. We further validated these DEGs in The Cancer Genome Atlas (TCGA) database and obtained Pearson's correlation coefficient (COR) for the relationship between gene expression and DNA methylation. Three candidate genes (SOX9, TCN1, and TGFBI) with COR greater than 0.3 were screened out as Hub genes. The receiver operating characteristic result indicated that SOX9 and TGFBI effectively serve as biomarkers for the early diagnosis of CRC. Furthermore, the potential prognosis of the Hub genes for CRC patients was evaluated. Only TGFBI, which is regulated by methylation, can predict patient disease‐free survival. Additionally, we examined the methylation level of the Hub genes in CRC cells in the Cancer Cell Line Encyclopedia database. Considering that methylation status tends to be highly modified on CpG islands in tumorigenesis, we screened the CpG island methylation of TGFBI based on the TCGA database and verified its diagnostic value in the GEO database. Our result revealed two Hub genes (TCN1 and TGFBI) whose aberrant expressions were regulated by DNA methylation. Additionally, we uncovered the hypermethylation of TGFBI on CpG islands and its clinical value in the diagnosis of CRC.
A LINC00341‐mediated regulatory pathway supports chondrocyte survival and may prevent osteoarthritis progression
Authors: Yang Qining , Li Xiaofei , Zhou Yongwei , Fu Weicong , Wang Jinhua , Wei Qiang
Published: January 2019

Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes. This is likely responsible for the increased apoptosis of chondrocytes and pathological destruction of cartilage. Further investigation has revealed that LINC00341 interacts with miR‐141 to suppress its functional binding to the 3′‐untranslated region of YY1‐associated factor 2 (YAF2) messenger RNA. Aberrant downregulation of LINC00341 thus may ultimately lead to inhibition of the YAF2 protein, which has been implicated to be an antiapoptotic factor. Our study has revealed a new noncoding RNA‐mediated regulatory network that highly likely protects chondrocytes by preventing apoptosis under normal conditions. The results will help further explore the molecular details pertaining to the progression of OA and stimulate efforts to develop effective therapies.
Instanton rate constant calculations using interpolated potential energy surfaces in nonredundant, rotationally and translationally invariant coordinates
Authors: McConnell Sean R. , Kästner Johannes
Published: January 2019

A trivial flaw in the utilization of artificial neural networks in interpolating chemical potential energy surfaces (PES) whose descriptors are Cartesian coordinates is their dependence on simple translations and rotations of the molecule under consideration. A different set of descriptors can be chosen to circumvent this problem, internuclear distances, inverse internuclear distances or z‐matrix coordinates are three such descriptors. The objective is to use an interpolated PES in instanton rate constant calculations, hence information on the energy, gradient, and Hessian is required at coordinates in the vicinity of the tunneling path. Instanton theory relies on smoothly fitted Hessians, therefore we use energy, gradients, and Hessians in the training procedure. A major challenge is presented in the proper back‐transformation of the output gradients and Hessians from internal coordinates to Cartesian coordinates. We perform comparisons between our method, a previous approach and on‐the‐fly rate constant calcuations on the hydrogen abstraction from methanol and on the hydrogen addition to isocyanic acid. © 2018Wiley Periodicals, Inc.
Deregulation of long noncoding RNA (TUG1) contributes to excessive podocytes apoptosis by activating endoplasmic reticulum stress in the development of diabetic nephropathy
Authors: Shen Hongchun , Ming Yao , Xu Chuanlan , Xu Yanwen , Zhao Sha , Zhang Qiong
Published: January 2019

The objective of this study was to investigate the molecular mechanism of how TUG1 interferes with the expression of C/EBP homologous protein (CHOP), peroxisome‐proliferator‐activated receptor‐γ coactivator‐1 alpha (PGC‐1α), which contributes to the development of diabetic nephropathy. Real‐time polymerase chain reaction and western blot analysis were performed to explore the regulatory relationship among TUG1, CHOP, PGC‐1α, and caspase‐3. Terminal deoxynucleotidyl transferase dUTP nick‐end labeling was performed to confirm TUG1 involved in diabetic nephropathy (DN) through influencing podocytes apoptosis. TUG1 was highly expressed in a cell following treatment with high glucose, and PGC‐1α and cleaved caspase‐3 levels were much lower, while CHOP level was much higher in high glucose group (HG), furthermore, CHOP inhibited PGC‐1α expression. TUG1 negatively regulated CHOP expression, and positively regulated PGC‐1α expression. Meanwhile, total caspase‐3 level in cell treated with or without HG transfected with CHOP small interfering ribonucleic acid (siRNA), TUG1, and TUG1 siRNA showed no evident difference with their corresponding control, while CHOP siRNA and TUG1 evidently decreased, and TUG1 siRNA remarkably increased cleaved caspase‐3 level in HG or normal glucose groups in comparison with corresponding control. TUG1 and PGC‐1α levels were much lower, while CHOP level was much higher in participants diagnosed with DN. A higher level of CHOP protein and lower level of PGC‐1α were observed in subjects diagnosed with DN. Finally, podocytes apoptosis in the DN group was significantly promoted compared with that in nondiabetic renal disease group. Our current study has suggested for the first time that the long noncoding RNA (lncRNA) TUG1 influenced podocytes apoptosis via mediating endoplasmic reticulum stress (ERS)–CHOP–PGC‐1α signaling pathway in HG‐induced DN.
A Monte Carlo method for comparing generalized estimating equations to conventional statistical techniques for discounting data
Authors: Friedel Jonathan E. , DeHart William B. , Foreman Anne M. , Andrew Michael E.
Published: January 2019

Discounting is the process by which outcomes lose value. Much of discounting research has focused on differences in the degree of discounting across various groups. This research has relied heavily on conventional null hypothesis significance tests that are familiar to psychologists, such as t‐tests and ANOVAs. As discounting research questions have become more complex by simultaneously focusing on within‐subject and between‐group differences, conventional statistical testing is often not appropriate for the obtained data. Generalized estimating equations (GEE) are one type of mixed‐effects model that are designed to handle autocorrelated data, such as within‐subject repeated‐measures data, and are therefore more appropriate for discounting data. To determine if GEE provides similar results as conventional statistical tests, we compared the techniques across 2,000 simulated data sets. The data sets were created using a Monte Carlo method based on an existing data set. Across the simulated data sets, the GEE and the conventional statistical tests generally provided similar patterns of results. As the GEE and more conventional statistical tests provide the same pattern of result, we suggest researchers use the GEE because it was designed to handle data that has the structure that is typical of discounting data.
Ammonia and autophagy: An emerging relationship with implications for disorders with hyperammonemia
Authors: Soria Leandro R. , Brunetti‐Pierri Nicola
Published: January 2019

(Macro)autophagy/autophagy is a highly regulated lysosomal degradative process by which cells recycle their own nutrients, such as amino acids and other metabolites, to be reused in different biosynthetic pathways. Ammonia is a diffusible compound generated daily from catabolism of nitrogen‐containing molecules and from gastrointestinal microbiome. Ammonia homeostasis is tightly controlled in humans and ammonia is efficiently converted by the healthy liver into non‐toxic urea (through ureagenesis) and glutamine (through glutamine synthetase). Impaired ammonia detoxification leads to systemic hyperammonemia, a life‐threatening condition resulting in detrimental effects on central nervous system. Here, we review current understanding on the role of ammonia in modulation of autophagy and the potential implications in the pathogenesis and treatment of disorders with hyperammonemia.
TREM-1 regulates neutrophil chemotaxis by promoting NOX-dependent superoxide production
Authors: Baruah Sankar , Murthy Shubha , Keck Kathy , Galvan Isabel , Prichard Allan , Allen Lee-Ann H , Farrelly Mary , Klesney-Tait Julia
Published: January 2019

Neutrophil migration across tissue barriers to the site of injury involves integration of complex danger signals and is critical for host survival. Numerous studies demonstrate that these environmental signals fundamentally alter the responses of extravasated or “primed” neutrophils. Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a central role in modulating inflammatory signaling and neutrophil migration into the alveolar airspace. Using a genetic approach, we examined the role of TREM-1 in extravasated neutrophil function. Neutrophil migration in response to chemoattractants is dependent upon multiple factors, including reactive oxygen species (ROS) generated either extracellularly by epithelial cells or intracellularly by NADPH oxidase (NOX). We, therefore, questioned whether ROS were responsible for TREM-1-mediated regulation of migration. Thioglycollate-elicited peritoneal neutrophils isolated from wild-type (WT) and TREM-1-deficient mice were stimulated with soluble and particulate agonists. Using electron paramagnetic resonance spectroscopy, we demonstrated that NOX2-dependent superoxide production is impaired in TREM-1-deficient neutrophils. Consistent with these findings, we confirmed with Clark electrode that TREM-1-deficient neutrophils consume less oxygen. Next, we demonstrated that TREM-1 deficient neutrophils have impaired directional migration to fMLP and zymosan-activated serum as compared to WT neutrophils and that deletion or inhibition of NOX2 in WT but not TREM-1-deficient neutrophils significantly impaired direction sensing. Finally, TREM-1 deficiency resulted in decreased protein kinase B (AKT) activation. Thus, TREM-1 regulates neutrophil migratory properties, in part, by promoting AKT activation and NOX2-dependent superoxide production. These findings provide the first mechanistic evidence as to how TREM-1 regulates neutrophil migration.
NK cell metabolism
Authors: Gardiner Clair M
Published: January 2019

Natural Killer (NK) cells are important antiviral and anticancer effector cells. They have excellent potential for immunotherapy although impaired functions during cancer limit their effectiveness. The discovery that cellular metabolism can impact on and regulate immune functions has led to an explosion of articles in this new area of immunometabolism. Metabolism has recently been shown to impact both murine and human NK cell biology. This review is targeted for newcomers to the field; it will introduce basic concepts in the area of immunometabolism including key aspects of glucose metabolism and mitochondrial function. It will review our current understanding of how metabolism of NK cells is differentially impacted in a variety of important situations. This is a rapidly expanding and exciting area of research that holds great potential for improving NK cell-based immunotherapies.
Ultrastructural and histochemical study of previtellogenic oogenesis in the desert lizard Scincus mitranus (Squamata, Sauropsida)
Authors: Aldokhi Othman A. , Alwasel Saleh , Harrath Abdel Halim
Published: January 2019

The structure of the granulosa in reptilian sauropsids varies between groups. We investigated the follicle development in the desert lizard Scincus mitranus. In the germinal bed, oogonia, and primary oocytes were identified and found to be interspersed between the epithelial cells. Previtellogenesis was divided into three stages: early, transitional, and late previtellogenic stages. During the early previtellogenic stage (diplotene), the oocyte is invested by small epithelia cells that formed a complete single layer, which may be considered as a young follicle. The transitional previtellogenic stage was marked by proliferation and differentiation of the granulosa layer from a homogenous layer consisting of only small cells to a heterogeneous layer containing three cell types: small, intermediate, and large cells. The late previtellogenic stage was marked by high‐synthetic activity of large cells and the initiation of cytoplasmic bridges between large granulosa cells and the oocyte. Small cells were the only type of granulosa cells that underwent division. Thus, these cells may be stem cells for the granulosa cell population and may develop into intermediate and subsequently large cells. The intermediate cells may be precursors of large cells, as suggested by their ultrastructure. The ultrastructure of the large granulosa was indicative of their high synthetic activity. Histochemical analysis indicated the presence of cholesterol and phospholipids in the cytoplasm of large cells, the zona pellucida, among the microvilli, in the bridges region, and in the cortical region of the oocyte cytoplasm. These materials may be transferred from large cells into the oocyte through cytoplasmic bridges and provide nutritive function to large cells rather than functioning in steroidogenesis or vitellogenesis.
Ion manipulation and enrichment mass spectrometer for cleavage of disulfide bond via ion/ion reaction
Authors: Ye Sijian , Li Ming , Jiang You , Gong Xiaoyun , Xiong Xingchuang , Liu Dajun , Zhao Bo , Fang Xiang
Published: January 2019

A novel mass spectrometer with the capability of ion manipulation and enrichment was developed to perform gas‐phase ion/ion reactions followed by product ions accumulation. The development of this apparatus opens opportunities for more complex sequences of ion manipulations, thus offers the potential on extensive application involving ion/ion reaction. Here, cleavage of disulfide bond in peptide was demonstrated based upon this ion manipulation and enrichment mass spectrometer. Two typical peptides including S‐glutathionylated ARACAKA with an intermolecular disulfide bond, and oxytocin with an intramolecular disulfide bond were chosen as typical samples to demonstrate the ability of the apparatus. After ion/ion reaction between selected peptide cations and periodate ions (IO4−), two kinds of product ions (eg, [M + O + H]+ and [M + H + Na + IO4]+) were enriched with a number of accumulation events. Afterwards, the enriched ions were subjected to activation, and the disulfide bond cleavage was clearly observed from the tandem mass spectra. These results illustrate the potential of this apparatus for ion manipulation performing ion/ion reaction, and low abundance product ion enrichment.
Is the placental proteome impaired in well‐controlled gestational diabetes?
Authors: Burlina Silvia , Banfi Cristina , Brioschi Maura , Visentin Silvia , Dalfrà Maria Grazia , Traldi Pietro , Lapolla Annunziata
Published: January 2019

In pregnancy complicated by gestational diabetes mellitus (GDM), the human placenta shows several pathological functional and structural changes, but the extent to which maternal glycemic control contributes to placental abnormalities remains unclear. The aim of this study was to profile and compare the proteome of placentas from healthy pregnant women and those with GDM, to investigate the placenta‐specific protein composition and possible changes of its function in presence of GDM. Quantitative proteomic analysis, based on LC‐MSE approach, revealed that higher (approximately 15% increase) levels of galectin 1 and collagen alpha‐1 XIV chain (although the difference regarding the latter was at the limit of significance) were present in GDM samples, while heat shock 70 kDa protein 1A/1B was less abundant in GDM placental tissue. These data seem to indicate that GDM, when well controlled, did not markedly affect the placental proteome.
Analytical performance of newly developed rapid point‐of‐care test for the simultaneous detection of hepatitis A, B, and C viruses in serum samples
Authors: Kweon Oh Joo , Lim Yong Kwan , Kim Hye Ryoun , Kim Tae‐Hyoung , Lee Mi‐Kyung
Published: January 2019

AbstractBackground

Although immunoassays play a major role in the detection of hepatitis viruses, there is a need for a point‐of‐care (POC) test. We evaluated the EuDx‐HE (A,B,C) kit (EUDIPIA, Cheongju, Korea), which detects anti‐hepatitis A virus (HAV) immunoglobulin M (IgM), hepatitis B virus surface antigen (HBsAg), and anti‐hepatitis C virus (HCV) immunoglobulin G (IgG) simultaneously using an immunochromatographic method within 15 minutes.

Methods

A total of 1581 serum samples including 57, 477, and 451 samples positive for anti‐HAV IgM, HBsAg, and anti‐HBV IgG, respectively, were analyzed. We investigated the diagnostic accuracy of the EuDx‐HE (A,B,C) kit by comparison with SD BIOLINE POC kits (Abbott, Chicago, IL) using Architect immunoassays as a reference method.

Results

For anti‐HAV IgM and HBsAg detection, the EuDx‐HE (A,B,C) kit showed a higher sensitivity and a slightly lower specificity than the SD BIOLINE kit. For anti‐HCV IgG detection, the EuDx‐HE (A,B,C) kit had a higher sensitivity and a higher specificity than the SD BIOLINE kit. The agreement for positivity between the POC tests was >89.47%, with κ values of 0.844, 0.941, and 0.943 for HAV, HBV, and HCV, respectively.

Conclusion

The EuDx‐HE (A,B,C) kit showed an acceptable clinical performance for detecting anti‐HAV IgM, HBsAg, and anti‐HCV.
Influence of stems and metaphyseal sleeve on primary stability of cementless revision tibial trays used to reconstruct AORI IIB defects
Authors: Awadalla Maged , Al‐Dirini Rami M. A. , O'Rourke Dermot , Solomon Lucian B. , Heldreth Mark , Rullkoetter Paul , Taylor Mark
Published: January 2019

Metaphyseal augments, such as sleeves, have been introduced to augment the fixation of revision total knee replacement (rTKR) components, and can be used with or without a stem. The effect of sleeve size in combination with stems on the primary stability and load transfer of a rTKR implant in AORI type IIB defects where the defect involves both condyles are poorly understood. The aim of this study was to examine the primary stability of revision tibial tray augmented with a sleeve in an AORI type IIB defect which involves both condyles with loss of cortical and cancellous bone. Finite element models were generated from computed tomography (CT) scans of nine individuals. All the bones used in the study had an AORI type IIB defect. The cohort included eight females (mean weight: 64 kg, height: 1.6 m). Material properties were sampled from CT data and assigned to the FE model. Joint contact forces for level gait, stair descent, and squat were applied. Stemless sleeved implants under various loading conditions were shown to have adequate primary stability in all AORI type IIB defects investigated. Adding a stem only marginally improved the primary stability of the implant but reduced the strain in the metaphysis compared to stemless implants. Once good initial mechanical stability was established with a sleeve, there was no benefit, in terms of primary stability or bone strains, from increasing sleeve size. This study suggests that metaphyseal sleeves, without a stem, can provide the required primary stability required by a rTKR tibial implant, to reconstruct an AORI type IIB defect. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Rapid characterization of the chemical constituents and rat metabolites of the Wen‐Jing decoction by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry
Authors: Xu Liu , Li Moying , Zhou Haifeng , Zhang Bei , Zhang Zhiqiang , Han Nina , Wu Tong
Published: January 2019

The Wen‐Jing decoction, a traditional Chinese medicine formula, has been used as a blood‐activating and stasis‐eliminating drug to treat gynaecological syndromes, such as dysmenorrhea, amenorrhea, and menstrual disorders. However, its pharmacodynamic material basis and mechanism of action have not been thoroughly elucidated to date. The goal of this study was to characterize and identify multiple constituents and metabolites in Wen‐Jing decoction. An ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry method was established and validated in the present study for the first time. A total of 101 compounds, including 11 monoterpene glycosides, 19 flavonoids, 49 triterpene saponins, 5 phthalides, 3 phytoecdysones, and 14 others, were unambiguously or tentatively characterized by comparing their retention times and MS data with reference standards or with data reported in the literature. After oral administration of Wen‐Jing decoction, 27 compounds, including nine prototype compounds and 18 metabolites were detected in rat plasma. Thus, the ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry method was found to be efficient for in‐depth structural elucidation of chemical compounds in complex matrices of herbal medicines, which will provide useful chemical information for quality control and mechanism‐of‐action research.
Facile synthesis of magnetic zinc metal‐organic framework for extraction of nitrogen‐containing heterocyclic fungicides from lettuce vegetable samples
Authors: Liu Guangyang , Huang Xiaodong , Lu Meng , Li Lingyun , Li Tengfei , Xu Donghui
Published: January 2019

We present a simple method for the fabrication of a magnetic amino‐functionalized zinc metal‐organic framework based on a magnetic graphene oxide composite. The resultant framework exhibited a porous 3D structure, high surface area and good adsorption properties for nitrogen‐containing heterocyclic fungicides. The adsorption process and capacity indicated that the primary adsorption mechanism might be hydrogen bonding and π‐π conjugation. In addition, an optimized protocol for magnetic solid phase extraction was developed (such as adsorbent content, pH, and desorption solvent), and utilized for the extraction of nitrogen‐containing heterocyclic fungicides from vegetable samples. Quantitation by high performance liquid chromatography coupled with tandem mass spectrometry offered a detection limit of 0.21–1.0 μg/L (S/N = 3) with correlation coefficients larger than 0.9975. These results demonstrate that magnetic amino‐functionalized zinc metal‐organic framewor is a promising adsorbent for the extraction and quantitation of nitrogen‐containing heterocyclic fungicides.
Do we need to move from communication technology to user community? A new economic model of the journal as a club
Authors: Hartley John , Potts Jason , Montgomery Lucy , Rennie Ellie , Neylon Cameron
Published: January 2019

Much of the argument around reforming, remaking, or preserving the traditions of scholarly publishing is built on economic principles, explicit or implicit. Can we afford open access (OA)? How do we pay for high‐quality services? Why does it cost so much? In this article, we argue that the sterility of much of this debate is a result of failure to tackle the question of what a journalisin economic terms. We offer a way through by demonstrating that a journal is a club and discuss the implications for the scholarly publishing industry. We use examples, ranging from OA to prestige journals, to explain why congestion is a problem for club‐based publications, and to discuss the importance of creative destruction for the maintenance of knowledge‐generating communities in publishing.
PLLA‐Grafted Gelatin Amphiphilic Copolymer and Its Self‐Assembled Nano Carrier for Anticancer Drug Delivery
Authors: Beibei Du , Tiantang Fan , Jiafeng Li , Li Gong , Qin Zhang , Wuyou Ye , Hongyun Tai , Wenxin Wang , Zhongyong Fan
Published: January 2019

A series of poly(l‐lactide)‐grafted gelatin (Gel‐g‐PLLA) copolymers are synthesized by coupling the amino groups of gelatin with different molar masses and the carboxyl endgroup of poly(l‐lactide) in the presence of 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride andN‐hydroxysuccinimide. Fourier transform infrared and nuclear magnetic resonance (1H NMR) data confirm the successful bonding between gelatin and PLLA. Self‐assembled micelles of copolymers are prepared by using the direct dissolution method. The size and micellar morphology are determined from dynamic light scattering as well as transmission electron microscopy measurements. Meanwhile, in vitro drug release reveals that Gel‐g‐PLLA micelles show excellent sustained‐release properties when used as the carrier of the anticancer drug paclitaxel. A burst release of about 70% is observed in the first 24 h. All these features, together with the outstanding biocompatibility, make Gel‐g‐PLLA micelles a promising drug carrier for cancer therapy.
A Robust Salty Water Adhesive by Counterion Exchange Induced Coacervate
Authors: Zhu Xiangwei , Wei Congying , Zhang Fang , Tang Qingquan , Zhao Qiang
Published: January 2019

Counterion exchange of charged macromolecules has comprehensive implications in biological and synthetic systems such as protein function, biosignaling, ion conducting, and separation, but the correlation between the dynamic ion exchange, polyelectrolyte phase separation, and functionality remains elusive. Here, counterion exchange is exploited as a means to facilitate liquid–liquid phase separation and coacervates featuring higher stability and versatility compared with conventional complex coacervate. Self‐coacervation of a cationic polyelectrolyte (polyamidoamine‐epichlorohydrin, PAE‐Cl) occurs in broader conditions when its original counter anion (Cl−) is exchanged by bis(trifluoromethane‐sulphonyl)imide anion (TFSI−), as a result of TFSI− counter anions association instead of polyelectrolyte complexation. This coacervate is catechol‐free, easy to prepare, and highlights robust wet adhesion strength on diverse submerged surfaces in salty water (pH = 3–11), as demonstrated by its versatile capability of in situ underwater gluing and repairing without any pre‐immersive drying.
Technical Note: Single‐shot phase retrieval method for synchrotron‐based high‐energy x‐ray grating interferometry
Authors: Wang Zhili , Ren Kun , Shi Xiaomin , Liu Dalin , Wu Zhao , Gao Kun
Published: January 2019

Purpose

X‐ray grating interferometry (XGI) provides substantially increased contrast over conventional absorption‐based imaging methods and therefore shows great potential for future biomedical applications. In this work, we propose a single‐shot phase retrieval method for synchrotron‐based high‐energy x‐ray grating interferometry. Contrary to existing retrieval methods, the presented novel approach enables direct retrieval of the object's phase map quantitatively from a single projection image, thus significantly simplifying the experimental procedure and reducing data acquisition times.

Methods

The phase retrieval method is analytically derived, based on the phase‐attenuation duality of soft tissues when being imaged with high‐energy x rays. The sensitivity of the retrieved phase map, quantified by the standard deviation, is evaluated as a function of the photon number. Numerical experiments are performed to validate the proposed method and provide some quantitative insight.

Results

The numerical results show that the method can provide high‐quality phase images, where the well‐known streak artifacts are significantly suppressed. Moreover, the retrieved phase maps confirm that the method is highly stable with respect to statistical noise.

Conclusions

Thanks to simplified experimental procedure and reduced acquisition time and dose deposition to the sample, we believe that this new method can find its potential in biomedical imaging and in vivo studies. Future work will focus on the adaptation of the method to polychromatic x ray from tube source and to computed tomography.