bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Ownership and Hospital Institutional Change: A Qualitative Study in Guizhou Province, China
Authors: Xie Yu , Liang Di , Huang Jiayan , Jin Jiajie
Published: April 2019

Objectives: To qualitatively compare the influence of different ownership which is considered as a kind of institutional environment in public hospitals, private hospitals, and mixed-ownership hospitals on hospital governance structure and organizational behavior. Design: Qualitative descriptive study, using semi-structured, in-depth interviews and thematic template analysis, theoretically informed by critical realism. Participants: 27 key informants including national policymakers in charge of the health sector, influential researchers, local administrators responsible for implementing policies, and hospital managers who are experienced in institutional change. Results: Hospital ownership has a significant influence on hospitals in terms of decision-making power allocation, residual ownership allocation, market entry level, accountability, and social functions. These five aspects in hospital organizational structure incentivize hospitals to adapt to the internal and external environment of the hospital organization—such as market environment, governance, and financing arrangements—affect the behavior of the hospital organization, and ultimately affect the efficiency of hospital operation and quality of service. The incentives under the public system are relatively distorted. Private hospitals have poor performance in failing their social functions due to their insufficient development ability. Compared to them, mixed ownership hospitals have a better performance in terms of incentive mechanism and organizational development. Conclusion: Public hospitals should improve the governance environment and decision-making structure, so as to balance their implementation of social functions and achieve favorable organizational development. For private hospitals, in addition to the optimization of the policy environment, attempts should be made to strengthen their supervision. The development of mixed-ownership hospitals should be oriented towards socialized governance.
Proteomics Reveal the Profiles of Color Change in Brunfelsia acuminata Flowers
Authors: Li Min , Sun Yueting , Lu Xiaocao , Debnath Biswojit , Mitra Sangeeta , Qiu Dongliang
Published: April 2019

Brunfelsia acuminata is a popular ornamental plant with different colors resulted from the rapid change of color after blooming. The petals at day one (purple), day three (white and purple) and day five (white) were used to analyze the reason of flower color change by a comparative proteomics approach, gas chromatography coupled to a time-of-flight mass analyzer (GC-TOF-MS) and quantitative real-time PCR (qRT-PCR). The results showed that the 52 identified proteins were classified into eight functional groups, 6% of which were related to the anthocyanin metabolic pathway. The expression levels of all anthocyanin proteins from the first day to fifth day were remarkably down-regulated, which was consistent with the changing patterns of the key genes (CHS, CHI and F3′5′H) in petals. Simultaneously, the main floral volatile components including Linalool and 2-Hexenal (E) were identified, and the contents of 2-Hexenal at day five increased dramatically. Moreover, the content of flavonoids and total phenolic increased at day five. The majority of the proteins associated with stress defense and senescence proteins were up-regulated and the activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) in the petals at day five were significantly higher than others. It was concluded that the competition in the precursors of metabolic pathways occurs and causes the flow of metabolite to the pathways of floral scent and lignin derived from the shikimate pathway or degrade into others. Therefore, the anthocyanin content significantly decreased, and the petal color changed from deep purple to white.
Biomarkers in Pneumonia—Beyond Procalcitonin
Authors: Karakioulaki Meropi , Stolz Daiana
Published: April 2019

Pneumonia is the leading infectious cause of mortality worldwide and one of the most common lower respiratory tract infections that is contributing significantly to the burden of antibiotic consumption. Due to the complexity of its pathophysiology, it is widely accepted that clinical diagnosis and prognosis are inadequate for the accurate assessment of the severity of the disease. The most challenging task for a physician is the risk stratification of patients with community-acquired pneumonia. Herein, early diagnosis is essential in order to reduce hospitalization and mortality. Procalcitonin and C-reactive protein remain the most widely used biomarkers, while interleukin 6 has been of particular interest in the literature. However, none of them appear to be ideal, and the search for novel biomarkers that will most sufficiently predict the severity and treatment response in pneumonia has lately intensified. Although our insight has significantly increased over the last years, a translational approach with the application of genomics, metabolomics, microbiomics, and proteomics is required to better understand the disease. In this review, we discuss this rapidly evolving area and summarize the application of novel biomarkers that appear to be promising for the accurate diagnosis and risk stratification of pneumonia.
The Protective Effect of Trichoderma asperellum on Tomato Plants against Fusarium oxysporum and Botrytis cinerea Diseases Involves Inhibition of Reactive Oxygen Species Production
Authors: Herrera-Téllez Verónica I. , Cruz-Olmedo Ana K. , Plasencia Javier , Gavilanes-Ruíz Marina , Arce-Cervantes Oscar , Hernández-León Sergio , Saucedo-García Mariana
Published: April 2019

Trichoderma species are fungi widely employed as plant-growth-promoting agents and for biological control. Several commercial and laboratory-made solid formulations for mass production of Trichoderma have been reported. In this study, we evaluated a solid kaolin-based formulation to promote the absortion/retention of Trichoderma asperellum in the substrate for growing tomato plants. The unique implementation of this solid formulation resulted in an increased growth of the tomato plants, both in roots and shoots after 40 days of its application. Plants were challenged with two fungal pathogens, Fusarium oxysporum and Botrytis cinerea, and pretreatment with T. asperellum resulted in less severe wilting and stunting symptoms than non-treated plants. Treatment with T. asperellum formulation inhibited Reactive Oxygen Species (ROS) production in response to the pathogens in comparison to plants that were only challenged with both pathogens. These results suggest that decrease in ROS levels contribute to the protective effects exerted by T. asperellum in tomato.
The Role of the Immune System in Cutaneous Squamous Cell Carcinoma
Authors: Bottomley Matthew J. , Thomson Jason , Harwood Catherine , Leigh Irene
Published: April 2019

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. In immunosuppressed populations it is a source of considerable morbidity and mortality due to its enhanced recurrence and metastatic potential. In common with many malignancies, leucocyte populations are both protective against cancer development and also play a role in ‘sculpting’ the nascent tumor, leading to loss of immunogenicity and tumor progression. UV radiation and chronic viral carriage may represent unique risk factors for cSCC development, and the immune system plays a key role in modulating the response to both. In this review, we discuss the lessons learned from animal and ex vivo human studies of the role of individual leucocyte subpopulations in the development of cutaneous SCC. We then discuss the insights into cSCC immunity gleaned from studies in humans, particularly in populations receiving pharmacological immunosuppression such as transplant recipients. Similar insights in other malignancies have led to exciting and novel immune therapies, which are beginning to emerge into the cSCC clinical arena.
Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers
Authors: Shahwar Durray , Iqbal Muhammad Javed , Nisa Mehr-un , Todorovska Milica , Attar Rukset , Sabitaliyevich Uteuliyev Yerzhan , Farooqi Ammad Ahmad , Ahmad Aamir , Xu Baojun
Published: April 2019

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.
Antimicrobial and Antibiofilm N-acetyl-L-cysteine Grafted Siloxane Polymers with Potential for Use in Water Systems
Authors: Kregiel Dorota , Rygala Anna , Kolesinska Beata , Nowacka Maria , Herc Agata S. , Kowalewska Anna
Published: April 2019

Antibiofilm strategies may be based on the prevention of initial bacterial adhesion, the inhibition of biofilm maturation or biofilm eradication. N-acetyl-L-cysteine (NAC), widely used in medical treatments, offers an interesting approach to biofilm destruction. However, many Eubacteria strains are able to enzymatically decompose the NAC molecule. This is the first report on the action of two hybrid materials, NAC-Si-1 and NAC-Si-2, against bacteria isolated from a water environment: Agrobacterium tumefaciens, Aeromonas hydrophila, Citrobacter freundii, Enterobacter soli, Janthinobacterium lividum and Stenotrophomonas maltophilia. The NAC was grafted onto functional siloxane polymers to reduce its availability to bacterial enzymes. The results confirm the bioactivity of NAC. However, the final effect of its action was environment- and strain-dependent. Moreover, all the tested bacterial strains showed the ability to degrade NAC by various metabolic routes. The NAC polymers were less effective bacterial inhibitors than NAC, but more effective at eradicating mature bacterial biofilms.
TRPM4 and TRPM5 Channels Share Crucial Amino Acid Residues for Ca2+ Sensitivity but Not Significance of PI(4,5)P2
Authors: Yamaguchi Soichiro , Tanimoto Akira , Iwasa Shinsuke , Otsuguro Ken-ichi
Published: April 2019

Transient receptor potential melastatin member 4 (TRPM4) and 5 (TRPM5) channels are Ca2+-activated nonselective cation channels. Intracellular Ca2+ is the most important regulator for them to open, though PI(4,5)P2, a membrane phosphoinositide, has been reported to regulate their Ca2+-sensitivities. We previously reported that negatively-charged amino acid residues near and in the TRP domain are necessary for the normal Ca2+ sensitivity of TRPM4. More recently, a cryo-electron microscopy structure of Ca2+-bound (but closed) TRPM4 was reported, proposing a Ca2+-binding site within an intracellular cavity formed by S2 and S3. Here, we examined the functional effects of mutations of the amino acid residues related to the proposed Ca2+-binding site on TRPM4 and also TRPM5 using mutagenesis and patch clamp techniques. The mutations of the amino acid residues of TRPM4 and TRPM5 reduced their Ca2+-sensitivities in a similar way. On the other hand, intracellular applications of PI(4,5)P2 recovered Ca2+-sensitivity of desensitized TRPM4, but its effect on TRPM5 was negligible. From these results, the Ca2+-binding sites of TRPM4 and TRPM5 were shown to be formed by the same amino acid residues by functional analyses, but the impact of PI(4,5)P2 on the regulation of TRPM5 seemed to be smaller than that on the regulation of TRPM4.
Polyaniline Functionalized Graphene Nanoelectrodes for the Regeneration of PC12 Cells via Electrical Stimulation
Authors: Zheng Zheng , Huang Libin , Yan Lu , Yuan Feng , Wang Lefeng , Wang Ke , Lawson Tom , Lin Mimi , Liu Yong
Published: April 2019

The regeneration of neurons is an important goal of neuroscience and clinical medicine. The electrical stimulation of cells is a promising technique to meet this goal. However, its efficiency highly depends on the electrochemical properties of the stimulation electrodes used. This work reports on the preparation and use of a highly electroactive and biocompatible nanoelectrode made from a novel polyaniline functionalized graphene composite. This nanocomposite was prepared using a facile and efficient polymerization-enhanced ball-milling method. It was used to stimulate the growth of PC12 cells under various electrical fields. The enhanced growth of axons and improved wound regeneration of PC12 cells were observed after this treatment, suggesting a promising strategy for neuro traumatology.
Benefits and Drawbacks of Harboring Plasmid pP32BP2, Identified in Arctic Psychrophilic Bacterium Psychrobacter sp. DAB_AL32B
Authors: Ciok Anna , Cegielski Adrian , Bartosik Dariusz , Dziewit Lukasz
Published: April 2019

Psychrobacter sp. DAB_AL32B, originating from Spitsbergen island (Arctic), carries the large plasmid pP32BP2 (54,438 bp). Analysis of the pP32BP2 nucleotide sequence revealed the presence of three predicted phenotypic modules that comprise nearly 30% of the plasmid genome. These modules appear to be involved in fimbriae synthesis via the chaperone-usher pathway (FIM module) and the aerobic and anaerobic metabolism of carnitine (CAR and CAI modules, respectively). The FIM module was found to be functional in diverse hosts since it facilitated the attachment of bacterial cells to abiotic surfaces, enhancing biofilm formation. The CAI module did not show measurable activity in any of the tested strains. Interestingly, the CAR module enabled the enzymatic breakdown of carnitine, but this led to the formation of the toxic by-product trimethylamine, which inhibited bacterial growth. Thus, on the one hand, pP32BP2 can enhance biofilm formation, a highly advantageous feature in cold environments, while on the other, it may prevent bacterial growth under certain environmental conditions. The detrimental effect of harboring pP32BP2 (and its CAR module) seems to be conditional, since this replicon may also confer the ability to use carnitine as an alternative carbon source, although a pathway to utilize trimethylamine is most probably necessary to make this beneficial. Therefore, the phenotype determined by this CAR-containing plasmid depends on the metabolic background of the host strain.
Targeting Platelet GPVI Plus rt-PA Administration but Not α2β1-Mediated Collagen Binding Protects against Ischemic Brain Damage in Mice
Authors: Schuhmann Michael K. , Kraft Peter , Bieber Michael , Kollikowski Alexander M. , Schulze Harald , Nieswandt Bernhard , Pham Mirko , Stegner David , Stoll Guido
Published: April 2019

Platelet collagen interactions at sites of vascular injuries predominantly involve glycoprotein VI (GPVI) and the integrin α2β1. Both proteins are primarily expressed on platelets and megakaryocytes whereas GPVI expression is also shown on endothelial and integrin α2β1 expression on epithelial cells. We recently showed that depletion of GPVI improves stroke outcome without increasing the risk of cerebral hemorrhage. Genetic variants associated with higher platelet surface integrin α2 (ITGA2) receptor levels have frequently been found to correlate with an increased risk of ischemic stroke in patients. However until now, no preclinical stroke study has addressed whether platelet integrin α2β1 contributes to the pathophysiology of ischemia/reperfusion (I/R) injury. Focal cerebral ischemia was induced in C57BL/6 and Itga2−/− mice by a 60 min transient middle cerebral artery occlusion (tMCAO). Additionally, wild-type animals were pretreated with anti-GPVI antibody (JAQ1) or Fab fragments of a function blocking antibody against integrin α2β1 (LEN/B). In anti-GPVI treated animals, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment was applied immediately prior to reperfusion. Stroke outcome, including infarct size and neurological scoring was determined on day 1 after tMCAO. We demonstrate that targeting the integrin α2β1 (pharmacologic; genetic) did neither reduce stroke size nor improve functional outcome on day 1 after tMCAO. In contrast, depletion of platelet GPVI prior to stroke was safe and effective, even when combined with rt-PA treatment. Our results underscore that GPVI, but not ITGA2, is a promising and safe target in the setting of ischemic stroke.
Ectopic Expression of a Fagopyrum esculentum APETALA1 Ortholog only Rescues Sepal Development in Arabidopsis ap1 Mutant
Authors: Liu Zhixiong , Fei Yue , Zhang Kebing , Fang Zhengwu
Published: April 2019

Fagopyrum esculentum (Polygonaceae: Caryophyllales) exhibits an undifferentiated perianth comprising five showy tepals, which does not completely correspond to the perianth differentiated into typical sepals and petals in most core eudicots. In Arabidopsis, the APETALA1 (AP1) gene is involved in specifying sepals and petals development. Here we isolated AP1 ortholog, FaesAP1, and a 2.2kb FaesAP1 promoter (pFaesAP1) from F. esculentum. FaesAP1 expression is mainly detectable in all floral organs and maintains at a high level when tepals elongate rapidly both in pin and thrum flowers. Moreover, the GUS reporter gene driven by pFaesAP1 was activated in flowers where the sepals were intense, but the petals very weak or absent. Additionally, FaesAP1 ectopic expression in Arabidopsis ap1-10 mutant rescues sepal development fully, obviously prompting early flowering, but failing to complement petal development. In this study, evidence was provided that the showy tepals in the F. esculentum are homologs to core eudicots sepals. Furthermore, these findings show a different perianth identity program in Caryophyllales, suggesting that AP1 orthologs involved in petal development may evolve independently across different clades of core eudicots. Our results also suggest that FaesAP1 holds potential for biotechnical engineering to develop early flowering varieties of F. esculentum.
Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs
Authors: Telkoparan-Akillilar Pelin , Suzen Sibel , Saso Luciano
Published: April 2019

Oxidative stress (OS) is associated with many diseases ranging from cancer to neurodegenerative disorders. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is one of the most effective cytoprotective controller against OS. Modulation of Nrf2 pathway constitutes a remarkable strategy in the antineoplastic treatments. A big number of Nrf2-antioxidant response element activators have been screened for use as chemo-preventive drugs in OS associated diseases like cancer even though activation of Nrf2 happens in a variety of cancers. Research proved that hyperactivation of the Nrf2 pathway produces a situation that helps the survival of normal as well as malignant cells, protecting them against OS, anticancer drugs, and radiotherapy. In this review, the modulation of the Nrf2 pathway, anticancer activity and challenges associated with the development of an Nrf2-based anti-cancer treatment approaches are discussed.
Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis
Authors: Joardar Swarnalata , Dewanjee Saikat , Bhowmick Shovonlal , Dua Tarun K. , Das Sonjit , Saha Achintya , De Feo Vincenzo
Published: April 2019

The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-β1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05–0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05–0.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.
Molecular Relationships among Obesity, Inflammation and Intervertebral Disc Degeneration: Are Adipokines the Common Link?
Authors: Ruiz-Fernández Clara , Francisco Vera , Pino Jesus , Mera Antonio , González-Gay Miguel Angel , Gómez Rodolfo , Lago Francisca , Gualillo Oreste
Published: April 2019

Intervertebral disc degeneration (IVDD) is a chronic, expensive, and high-incidence musculoskeletal disorder largely responsible for back/neck and radicular-related pain. It is characterized by progressive degenerative damage of intervertebral tissues along with metabolic alterations of all other vertebral tissues. Despite the high socio-economic impact of IVDD, little is known about its etiology and pathogenesis, and currently, no cure or specific treatments are available. Recent evidence indicates that besides abnormal and excessive mechanical loading, inflammation may be a crucial player in IVDD. Furthermore, obese adipose tissue is characterized by a persistent and low-grade production of systemic pro-inflammatory factors. In this context, chronic low-grade inflammation associated with obesity has been hypothesized as an important contributor to IVDD through different, but still unknown, mechanisms. Adipokines, such as leptin, produced prevalently by white adipose tissues, but also by other cells of mesenchymal origin, particularly cartilage and bone, are cytokine-like hormones involved in important physiologic and pathophysiological processes. Although initially restricted to metabolic functions, adipokines are now viewed as key players of the innate and adaptative immune system and active modulators of the acute and chronic inflammatory response. The goal of this review is to summarize the most recent findings regarding the interrelationships among inflammation, obesity and the pathogenic mechanisms involved in the IVDD, with particular emphasis on the contribution of adipokines and their potential as future therapeutic targets.
New ND-FISH-Positive Oligo Probes for Identifying Thinopyrum Chromosomes in Wheat Backgrounds
Authors: Xi Wei , Tang Zongxiang , Tang Shuyao , Yang Zujun , Luo Jie , Fu Shulan
Published: April 2019

Thinopyrum has been widely used to improve wheat (Triticum aestivum L.) cultivars. Non-denaturing fluorescence in situ hybridization (ND-FISH) technology using oligonucleotides (oligo) as probes provides a convenient and efficient way to identify alien chromosomes in wheat backgrounds. However, suitable ND-FISH-positive oligo probes for distinguishing Thinopyrum chromosomes from wheat are lacking. Two oligo probes, Oligo-B11 and Oligo-pThp3.93, were designed according to the published Thinopyrum ponticum (Th. ponticum)-specific repetitive sequences. Both Oligo-B11 and Oligo-pThp3.93 can be used for ND-FISH analysis and can replace conventional GISH and FISH to discriminate some chromosomes of Th. elongatum, Th. intermedium, and Th. ponticum in wheat backgrounds. The two oligo probes provide a convenient way for the utilization of Thinopyrum germplasms in future wheat breeding programs.
The Role of ApoE in HCV Infection and Comorbidity
Authors: Gong Yue , Cun Wei
Published: April 2019

Hepatitis C virus (HCV) is an RNA virus that can efficiently establish chronic infection in humans. The overlap between the HCV replication cycle and lipid metabolism is considered to be one of the primary means by which HCV efficiently develops chronic infections. In the blood, HCV is complex with lipoproteins to form heterogeneous lipo-viro-particles (LVPs). Furthermore, apolipoprotein E (ApoE), which binds to receptors during lipoprotein transport and regulates lipid metabolism, is localized on the surface of LVPs. ApoE not only participate in the attachment and entry of HCV on the cell surface but also the assembly and release of HCV viral particles from cells. Moreover, in the blood, ApoE can also alter the infectivity of HCV and be used by HCV to escape recognition by the host immune system. In addition, because ApoE can also affect the antioxidant and immunomodulatory/anti-inflammatory properties of the host organism, the long-term binding and utilization of host ApoE during chronic HCV infection not only leads to liver lipid metabolic disorders but may also lead to increased morbidity and mortality associated with systemic comorbidities.
Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells
Authors: Masoumi Zahra , Maes Gregory E. , Herten Koen , Cortés-Calabuig Álvaro , Alattar Abdul Ghani , Hanson Eva , Erlandsson Lena , Mezey Eva , Magnusson Mattias , Vermeesch Joris R , Familari Mary , Hansson Stefan R
Published: April 2019

Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.
Distinct Binding Dynamics, Sites and Interactions of Fullerene and Fullerenols with Amyloid-β Peptides Revealed by Molecular Dynamics Simulations
Authors: Liu Zhiwei , Zou Yu , Zhang Qingwen , Chen Peijie , Liu Yu , Qian Zhenyu
Published: April 2019

The pathology Alzheimer’s disease (AD) is associated with the self-assembly of amyloid-β (Aβ) peptides into β-sheet enriched fibrillar aggregates. A promising treatment strategy is focused on the inhibition of amyloid fibrillization of Aβ peptide. Fullerene C60 is proved to effectively inhibit Aβ fibrillation while the poor water-solubility restricts its use as a biomedicine agent. In this work, we examined the interaction of fullerene C60 and water-soluble fullerenol C60(OH)6/C60(OH)12 (C60 carrying 6/12 hydroxyl groups) with preformed Aβ40/42 protofibrils by multiple molecular dynamics simulations. We found that when binding to the Aβ42 protofibril, C60, C60(OH)6 and C60(OH)12 exhibit distinct binding dynamics, binding sites and peptide interaction. The increased number of hydroxyl groups C60 carries leads to slower binding dynamics and weaker binding strength. Binding free energy analysis demonstrates that the C60/C60(OH)6 molecule primarily binds to the C-terminal residues 31–41, whereas C60(OH)12 favors to bind to N-terminal residues 4–14. The hydrophobic interaction plays a critical role in the interplay between Aβ and all the three nanoparticles, and the π-stacking interaction gets weakened as C60 carries more hydroxyls. In addition, the C60(OH)6 molecule has high affinity to form hydrogen bonds with protein backbones. The binding behaviors of C60/C60(OH)6/C60(OH)12 to the Aβ40 protofibril resemble with those to Aβ42. Our work provides a detailed picture of fullerene/fullerenols binding to Aβ protofibril, and is helpful to understand the underlying inhibitory mechanism.
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations
Authors: Świerczewska Monika , Sterzyńska Karolina , Wojtowicz Karolina , Kaźmierczak Dominika , Iżycki Dariusz , Nowicki Michał , Zabel Maciej , Januchowski Radosław
Published: April 2019

Background: Ovarian cancer is the 7th most common cancer and 8th most mortal cancer among woman. The standard treatment includes cytoreduction surgery followed by chemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance. Decreased expression and/or activity of protein phosphatases leads to increased signal transduction and development of drug resistance in cancer cells. Methods: Using sensitive (W1, A2780) and resistant ovarian cancer cell lines, the expression of Protein Tyrosine Phosphatase Receptor Type K (PTPRK) was performed at the mRNA (real-time PCR analysis) and protein level (Western blot, immunofluorescence analysis). The protein expression in ovarian cancer tissues was determined by immunohistochemistry. Results: The results showed a decreased level of PTPRK expression in ovarian cancer cell lines resistant to cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), topotecan (TOP), vincristine (VIN) and methotrexate (MTX). Additionally, the lower PTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation in primary as well as acquired resistance to cytotoxic drugs. Conclusions: These results provide important insights into the role of PTPRK in mechanism leading to drug resistance in ovarian cancer and has raised important questions about the role of imbalance in processes of phosphorylation and dephosphorylation.
MDS Self-Dual Codes and Antiorthogonal Matrices over Galois Rings
Authors: Han Sunghyu
Published: April 2019

In this study, we explore maximum distance separable (MDS) self-dual codes over Galois rings G R ( p m , r ) with p ≡ − 1 ( mod 4 ) and odd r. Using the building-up construction, we construct MDS self-dual codes of length four and eight over G R ( p m , 3 ) with ( p = 3 and m = 2 , 3 , 4 , 5 , 6 ), ( p = 7 and m = 2 , 3 ), ( p = 11 and m = 2 ), ( p = 19 and m = 2 ), ( p = 23 and m = 2 ), and ( p = 31 and m = 2 ). In the building-up construction, it is important to determine the existence of a square matrix U such that U U T = − I , which is called an antiorthogonal matrix. We prove that there is no 2 × 2 antiorthogonal matrix over G R ( 2 m , r ) with m ≥ 2 and odd r.
Prevention of Sudden Death Related to Sport: The Science of Basic Life Support—From Theory to Practice
Authors: Vancini Rodrigo Luiz , Nikolaidis Pantelis Theodoros , de Lira Claudio Andre Barbosa , Vancini-Campanharo Cássia Regina , Viana Ricardo Borges , Andrade Marilia dos Santos , Rosemann Thomas , Knechtle Beat
Published: April 2019

The sudden cardiac arrest (CA) and death of athletes are dramatic and emotionally impacting events for health professionals, family, and society. Although the practice of sport participation improves general health, physical fitness, and quality of life, intense physical exercise can be a trigger for CA and sudden death occasionally in the presence of known or unknown cardiac disorders (mainly hypertrophic cardiomyopathy) and risk factors (environment, health style, family, and genetic). The present review found that sudden death associated with CA was not such a common event in competitive athletes, but it might be an underestimated event in recreational athletes. Thus, considering the exponential increase in sport participation, both in a recreational or competitive way, and the rate of sudden CA, knowledge of implementing prevention and treatment strategies is crucial. This includes preparation of health professionals and lay people in basic life support (BLS); screening and pre-participation assessment in sport programs and health education; and promotion for the recognition of CA and early completion of BLS and rapid access to automatic external defibrillator to improve the victim survival/prognosis. Thus, the purpose of this review is to provide for health professionals and lay people the most updated information, based on current guidelines, of how to proceed in an emergency situation associated with sudden CA of young adult athletes.
Mismatch Repair/Microsatellite Instability Testing Practices among US Physicians Treating Patients with Advanced/Metastatic Colorectal Cancer
Authors: Eriksson Jennifer , Amonkar Mayur , Al-Jassar Gemma , Lambert Jeremy , Malmenäs Mia , Chase Monica , Sun Lucy , Kollmar Linda , Vichnin Michelle
Published: April 2019

The study objective was to assess US physicians’ Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. Eligible physicians were US-based with at least 5 years of experience treating CRC patients, had at least one mCRC patient in their routine care in the past 6 months, and had ordered at least one MMR/MSI test for CRC in the past 6 months. Descriptive and logistic regression analyses were performed. Awareness of specific MMR/MSI testing guidelines was high (n = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of National Comprehensive Cancer Network (NCCN) guidelines. Universal testing for all CRC patients was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively order the test for some CRC patients. Key barriers for testing included insufficient tissue sample (48.3%, 73/151), patient declined to have the test done (35.8%, 54/151) and insurance cost concerns for patients (31.1%, 47/151), while 27.2% (41/151) reported no barriers. The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal.
Biomarkers in the Diagnosis, Management, and Prognostication of Perioperative Right Ventricular Failure in Cardiac Surgery—Are We There Yet?
Authors: Jabagi Habib , Mielniczuk Lisa M. , Liu Peter P. , Ruel Marc , Sun Louise Y.
Published: April 2019

Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few studies have examined the use of biomarkers in RVF, and even fewer have examined their utility in the perioperative setting of patients undergoing cardiac surgery. Of the available classes of biomarkers, this review focuses on biomarkers of (1) inflammation and (2) myocyte injury/stress, due to their superior potential in perioperative RV assessment, including Galectin 3, ST2/sST2, CRP, cTN/hs-cTn, and BNP/NT-proBNP. This review was performed to help highlight the importance of perioperative RV function in patients undergoing cardiac surgery, to review the current modalities of RV assessment, and to provide a review of RV specific biomarkers and their potential utilization in the clinical and perioperative setting in cardiac surgery. Based on current evidence, we suggest the potential utility of ST2, sST2, Gal-3, CRP, hs-cTn, and NT-proBNP in predicting and detecting RVF in cardiac surgery patients, as they encompass the multifaceted nature of perioperative RVF and warrant further investigation to establish their clinical utility.
UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition
Authors: Martinez-Useros Javier , Garcia-Carbonero Nuria , Li Weiyao , Fernandez-Aceñero Maria , Cristobal Ion , Rincon Raul , Rodriguez-Remirez Maria , Borrero-Palacios Aurea , Garcia-Foncillas Jesus
Published: April 2019

CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.
Acid-Base Disturbances in Patients with Asthma: A Literature Review and Comments on Their Pathophysiology
Authors: Vasileiadis Ioannis , Alevrakis Emmanouil , Ampelioti Sevasti , Vagionas Dimitrios , Rovina Nikoletta , Koutsoukou Antonia
Published: April 2019

Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the resulting hypoxemia along with the circulatory compromise due to heart–lung interactions can reduce tissue oxygenation, with a particular impact on respiratory muscles that have increased energy needs due to the increased workload. Thus, anaerobic metabolism may ensue, leading to lactic acidosis. Additionally, chronic hypocapnia in asthma can cause a compensatory drop in plasma bicarbonate concentration, resulting in non-anion gap acidosis. Indeed, studies have shown that in acute severe asthma, metabolic acid-base disorders may occur, i.e., high anion gap or non-anion gap metabolic acidosis. This review briefly presents studies that have investigated acid-base disorders in asthma, with comments on their underlying pathophysiology.
A Threshold of Objectively-Assessed Daily Sedentary Time for All-Cause Mortality in Older Adults: A Meta-Regression of Prospective Cohort Studies
Authors: Ku Po-Wen , Steptoe Andrew , Liao Yung , Hsueh Ming-Chun , Chen Li-Jung
Published: April 2019

Background: This meta-analysis aimed to estimate the shape of the dose-response association between objectively-assessed daily sedentary time (ST) and all-cause mortality, and to explore whether there is a threshold of ST above which there is an increase in mortality risk in older adults. Methods: Searches for prospective cohort studies providing effect estimates of daily ST (exposure) on all-cause mortality (outcome) were undertaken in five databases up to 31 March 2019. A random-effects meta-regression model was conducted to quantify the dose-response relationship between daily ST and all-cause mortality. Sensitivity analyses were also performed to test the stability of the results. Results: Our analysis of pooled data from 11 eligible studies did not reveal a consistent shape of association between ST and mortality. After excluding three studies with potential confounding bias, there was a log-linear dose-response relationship between daily ST and all-cause mortality. Overall, higher amounts of time spent in sedentary behaviors were associated with elevated mortality risks in older adults. Visual assessments of dose-response relationships based on meta-regression analyses indicated that increased mortality risks became significant when total ST exceeded approximately 9 h/day. Conclusions: Based on a limited number of studies, this meta-analysis provides a starting point for considering a cut-off of daily sedentary time, suggesting older adults spend less time in daily sitting.
Biomass-Templated Fabrication of Metallic Materials for Photocatalytic and Bactericidal Applications
Authors: Guo Xueying , Wang Qianqian , Lai Qiongyu , Ouyang Qiran , Li Peng , Yu Hai-Dong , Huang Wei
Published: April 2019

In this paper, we report a simple, feasible and low-cost method to fabricate self-standing metallic materials using cellulose-based biomass as sacrificial templates. This process involves the impregnation of metallic precursors to the cellulose fibers of biomass templates and the transformation of the precursors to corresponding metals or metal oxides (as well as the removal of the cellulose framework) at an elevated temperature. The structures of the metallic materials as fabricated take the form of architectures of biomass templates (e.g., chromatography paper, medical absorbent cotton, catkins of reed, seed balls of oriental plane, and petals of peach blossom), and the various kinds of metals and metal oxides fabricated with these templates include silver, gold, anatase, cupric oxide, zinc oxide, etc. We have demonstrated photocatalytic and bactericidal applications of such metallic materials, and they should find more applications in electronics, catalysis, energy storage, biomedicine and so on.
New Numerical Results from Simulations of Beams and Space Frame Systems with a Tuned Mass Damper
Authors: Tho Nguyen Chi , Ta Nguyen Tri , Thom Do Van
Published: April 2019

In working processes, mechanical systems are often affected by both internal and external forces, which are the cause of the forced vibrations of the structures. They can be destroyed if the amplitude of vibration reaches a high enough value. One of the most popular ways to reduce these forced vibrations is to attach tuned mass damper (TMD) devices, which are commonly added at the maximum displacement point of the structures. This paper presents the computed results of the free vibration and the vibration response of the space frame system under an external random load, which is described as a stationary process with white noise. Static and dynamic equations are formed through the finite element method. In addition, this work also establishes artificial neural networks (ANNs) in order to predict the vibration response of the first frequencies of the structure. Numerical studies show that the data set of the TMD device strongly affects the first frequencies of the mechanical system, and the proposed artificial intelligence (AI) model can predict exactly the vibration response of the first frequencies of the structure. For the forced vibration problem, we can find optimal parameters of the TMD device and thus obtain minimum displacements of the structure. The results of this work can be used as a reference when applying this type of structure to TMD devices.
Old Molecule, New Chemistry: Exploring Silicon Phthalocyanines as Emerging N-Type Materials in Organic Electronics
Authors: Yutronkie Nathan J. , Grant Trevor M. , Melville Owen A. , Lessard Benoît H. , Brusso Jaclyn L.
Published: April 2019

Efficient synthesis of silicon phthalocyanines (SiPc) eliminating the strenuous reaction conditions and hazardous reagents required by classical methods is described. Implementation into organic thin-film transistors (OTFTs) affords average electron field-effect mobility of 3.1 × 10−3 cm2 V−1 s−1 and threshold voltage of 25.6 V for all synthetic routes. These results demonstrate that our novel chemistry can lead to high performing SiPc-based n-type OTFTs.
Experimental and Theoretical Studies on the Corrosion Inhibition of Carbon Steel by Two Indazole Derivatives in HCl Medium
Authors: Xu Shenying , Zhang Shengtao , Guo Lei , Feng Li , Tan Bochuan
Published: April 2019

In this work, two indazole derivatives, namely 5-aminoindazole (AIA) and 5-nitroindazole (NIA), were investigated as corrosion inhibitors for carbon steel in 1 M HCl solution by experimental and density functional theory (DFT) methods. The electrochemical results indicate that the inhibition ability follows the order of AIA > NIA, which is due to the stronger electron-donating effect of –NH2 of the AIA group than the –NO2 group of NIA. Besides, the frontier orbital theory shows that the AIA exhibits higher reaction activity than NIA, and a more negative adsorption energy for AIA was also obtained, which is consistent with the analysis of the electrochemical measurements. We draw the conclusion that the electron-donating effect makes it easier for AIA to donate electrons to iron atoms to form a stronger protective layer than NIA.
Simulation and Experimental Study on Residual Stress Distribution in Titanium Alloy Treated by Laser Shock Peening with Flat-Top and Gaussian Laser Beams
Authors: Li Xiang , He Weifeng , Luo Sihai , Nie Xiangfan , Tian Le , Feng Xiaotai , Li Rongkai
Published: April 2019

The residual stress introduced by laser shock peening (LSP) is one of the most important factors in improving metallic fatigue life. The shock wave pressure has considerable influence on residual stress distribution, which is affected by the distribution of laser energy. In this work, a titanium alloy is treated by LSP with flat-top and Gaussian laser beams, and the effects of spatial energy distribution on residual stress are investigated. Firstly, a 3D finite element model (FEM) is developed to predict residual stress with different spatial energy distribution, and the predicted residual stress is validated by experimental data. Secondly, three kinds of pulse energies, 3 J, 4 J and 5 J, are chosen to study the difference of residual stress introduced by flat-top and Gaussian laser beams. Lastly, the effect mechanism of spatial energy distribution on residual stress is revealed.