bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Residential Green and Blue Space Promote Recovery in Psychotic Disorders? A Cross-Sectional Study in the Province of Utrecht, The Netherlands
Authors: Boers Susanne , Hagoort Karin , Scheepers Floortje , Helbich Marco
Published: October 2018

Mental health is reportedly influenced by the presence of green and blue space in residential areas, but scientific evidence of a relation to psychotic disorders is scant. We put two hypotheses to the test: first, compared to the general population, psychiatric patients live in neighborhoods with less green and blue space; second, the amount of green and blue space is negatively associated with the duration of hospital admission. The study population consisted of 623 patients with psychotic disorders who had been admitted to the psychiatric ward of an academic hospital in Utrecht, The Netherlands from 2008 to 2016. Recovery was measured by length of stay. Structured patient data was linked to socio-economic status and the amount of green and blue space in the residential area. Associations were assessed by means of regression models controlling for confounding factors. Compared to the general population, psychiatric patients had a significantly lower amount of green space in their neighborhood. This result was not confirmed for blue space. Furthermore, no significant associations were found between green and blue space and the duration of hospital stay. In conclusion, previous studies focusing on other mental disorders, like anxiety or depression, found positive mental health effects of green and blue space in the neighborhood. We were not able to confirm significant effects among our study population on duration of admission, however. Future research focusing on psychotic patients could investigate the influence of exposure to green and blue space on other influences and outcomes on mental health.
Editorial for Special Issue “Finance, Financial Risk Management and their Applications”
Authors: Chan Leunglung
Published: October 2018

We are pleased to announce the Special Issue on the Finance, Financial Risk Management and their Applications in the International Journal of Financial Studies. This Special Issue collects papers pertaining to several lines of research related to finance and financial risks. This Guest Editor’s note synthesizes the contributing authors’ propositions and findings regarding these developments and hopes that new areas can be opened for future researches.
Variations in Physiology and Multiple Bioactive Constituents under Salt Stress Provide Insight into the Quality Evaluation of Apocyni Veneti Folium
Authors: Chen Cuihua , Wang Chengcheng , Liu Zixiu , Liu Xunhong , Zou Lisi , Shi Jingjing , Chen Shuyu , Chen Jiali , Tan Mengxia
Published: October 2018

As one of the major abiotic stresses, salinity stress may affect the physiology and biochemical components of Apocynum venetum L. To systematically evaluate the quality of Apocyni Veneti Folium (AVF) from the perspective of physiological and the wide variety of bioactive components response to various concentrations of salt stress, this experiment was arranged on the basis of ultra-fast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-QTRAP-MS/MS) technology and multivariate statistical analysis. Physiological characteristics of photosynthetic pigments, osmotic homeostasis, lipid peroxidation product, and antioxidative enzymes were introduced to investigate the salt tolerance mechanism of AVF under salinity treatments of four concentrations (0, 100, 200, and 300 mM NaCl, respectively). Furthermore, a total of 43 bioactive constituents, including 14 amino acids, nine nucleosides, six organic acids, and 14 flavonoids were quantified in AVF under salt stress. In addition, multivariate statistical analysis, including hierarchical clustering analysis, principal component analysis (PCA), and gray relational analysis (GRA) was employed to systematically cluster, distinguish, and evaluate the samples, respectively. Compared with the control, the results demonstrated that 200 mM and 100 mM salt stress contributed to maintain high quality of photosynthesis, osmotic balance, antioxidant enzyme activity, and the accumulation of metabolites, except for total organic acids, and the quality of AVF obtained by these two groups was better than others; however, under severe stress, the accumulation of the oxidative damage and the reduction of metabolite caused by inefficiently scavenging reactive oxygen species (ROS) lead to lower quality. In summary, the proposed method may provide integrated information for the quality evaluation of AVF and other salt-tolerant Chinese medicines.
MDA-MB-231 Breast Cancer Cells and Their CSC Population Migrate Towards Low Oxygen in a Microfluidic Gradient Device
Authors: Sleeboom Jelle J. F. , Den Toonder Jaap M. J. , Sahlgren Cecilia M.
Published: October 2018

Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.
Lung Diseases: Chronic Respiratory Infections
Authors: Blasi Francesco
Published: October 2018

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Resveratrol Attenuates Staphylococcus Aureus-Induced Monocyte Adhesion through Downregulating PDGFR/AP-1 Activation in Human Lung Epithelial Cells
Authors: Lee I-Ta , Lin Chih-Chung , Yang Chien-Chung , Hsiao Li-Der , Wu Ming-Yen , Yang Chuen-Mao
Published: October 2018

Staphylococcus aureus (S. aureus) is a very common Gram-positive bacterium. It is widely distributed in air, soil, and water. S. aureus often causes septicemia and pneumonia in patients. In addition, it is considered to play a key role in mediating cell adhesion molecules upregulation. Resveratrol is a natural antioxidant with diverse biological effects, including the modulation of immune function, anti-inflammation, and cancer chemoprevention. In this study, we proved that S. aureus-upregulated vascular cell adhesion molecule-1 (VCAM-1) expression in human lung epithelial cells (HPAEpiCs) was inhibited by resveratrol. We also observed that resveratrol downregulated S. aureus-enhanced leukocyte count in bronchoalveolar lavage (BAL) fluid in mice. In HPAEpiCs, S. aureus stimulated c-Src, PDGFR, p38 MAPK, or JNK1/2 phosphorylation, which was inhibited by resveratrol. S. aureus induced the adhesion of THP-1 cells (a human monocytic cell line) to HPAEpiCs, which was also reduced by resveratrol. Finally, we found that S. aureus induced c-Src/PDGFR/p38 MAPK and JNK1/2-dependent c-Jun and ATF2 activation and in vivo binding of c-Jun and ATF2 to the VCAM-1 promoter, which were inhibited by resveratrol. Thus, resveratrol functions as a suppressor of S. aureus-induced inflammatory signaling, not only by inhibiting VCAM-1 expression but also by diminishing c-Src, PDGFR, JNK1/2, p38 MAPK, and AP-1 activation in HPAEpiCs.
Enhancing Skin Health: By Oral Administration of Natural Compounds and Minerals with Implications to the Dermal Microbiome
Authors: Vollmer David L. , West Virginia A. , Lephart Edwin D.
Published: October 2018

The history of cosmetics goes back to early Egyptian times for hygiene and health benefits while the history of topical applications that provide a medicinal treatment to combat dermal aging is relatively new. For example, the term cosmeceutical was first coined by Albert Kligman in 1984 to describe topical products that afford both cosmetic and therapeutic benefits. However, beauty comes from the inside. Therefore, for some time scientists have considered how nutrition reflects healthy skin and the aging process. The more recent link between nutrition and skin aging began in earnest around the year 2000 with the demonstrated increase in peer-reviewed scientific journal reports on this topic that included biochemical and molecular mechanisms of action. Thus, the application of: (a) topical administration from outside into the skin and (b) inside by oral consumption of nutritionals to the outer skin layers is now common place and many journal reports exhibit significant improvement for both on a variety of dermal parameters. Therefore, this review covers, where applicable, the history, chemical structure, and sources such as biological and biomedical properties in the skin along with animal and clinical data on the oral applications of: (a) collagen, (b) ceramide, (c) β-carotene, (d) astaxanthin, (e) coenzyme Q10, (f) colostrum, (g) zinc, and (h) selenium in their mode of action or function in improving dermal health by various quantified endpoints. Lastly, the importance of the human skin microbiome is briefly discussed in reference to the genomics, measurement, and factors influencing its expression and how it may alter the immune system, various dermal disorders, and potentially be involved in chemoprevention.
Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells
Authors: To Phuong Kim , Do Manh-Hung , Cho Young-Suk , Kwon Se-Young , Kim Min Soo , Jung Chaeyong
Published: October 2018

The prostate gland contains a high level of intracellular zinc, which is dramatically diminished during prostate cancer (PCa) development. Owing to the unclear role of zinc in this process, therapeutic applications using zinc are limited. This study aimed to clarify the role of zinc and its underlying mechanism in the growth of PCa. ZnCl2 suppressed the proliferation of androgen receptor (AR)-retaining PCa cells, whereas it did not affect AR-deficient PCa cells. In LNCaP and TRAMP-C2 cells, zinc downregulated the expression of AR in a dose- and time-dependent fashion. Zinc-mediated AR suppression accordingly inhibited the androgen-mediated transactivation and expression of the androgen target, prostate specific antigen (PSA). This phenomenon resulted from facilitated protein degradation, not transcriptional control. In studies using mice bearing TRAMP-C2 subcutaneous tumors, the intraperitoneal injection of zinc significantly reduced tumor size. Analyses of both xenograft tumors and normal prostates showed reduced expression of AR and increased cell death. Considering the significant loss of intracellular zinc and the dominant growth-modulating role of AR during PCa development, loss of zinc may be a critical step in the transformation of normal cells to cancer cells. This study provides the underlying mechanism by which zinc functions as a PCa suppressor, and forms the foundation for developing zinc-mediated therapeutics for PCa.
Pain in Mucopolysaccharidoses: Analysis of the Problem and Possible Treatments
Authors: Congedi Sabrina , Orzalesi Marcello , Di Pede Chiara , Benini Franca
Published: October 2018

Mucopolysaccharidosis (MPS) are a group of lysosomal storage disorders that are caused by the deficiency of enzymes involving in the catabolism of glycosaminoglycan (GAGs). GAGs incompletely degraded accumulate in many sites, damaging tissues and cells, leading to a variety of clinical manifestations. Many of these manifestations are painful, but few data are available in the literature concerning the prevalence, etiology, and pathogenesis of pain in children with MPS. This review, through the analysis of the data available the in literature, underscores the relevant prevalence of pain in MPSs’ children, provides the instruments to discern the etiopathogenesis of the disease and of pain, illustrates the available molecules for the management of pain and the possible advantages of non-pharmacological pain therapy in MPSs’ patients.
Transcriptome Sequencing Reveals the Differentially Expressed lncRNAs and mRNAs Involved in Cryoinjuries in Frozen-Thawed Giant Panda (Ailuropoda melanoleuca) Sperm
Authors: Ran Ming-Xia , Li Yuan , Zhang Yan , Liang Kai , Ren Ying-Nan , Zhang Ming , Zhou Guang-Bin , Zhou Ying-Min , Wu Kai , Wang Cheng-Dong , Huang Yan , Luo Bo , Qazi Izhar , Zhang He-Min , Zeng Chang-Jun
Published: October 2018

Sperm cryopreservation and artificial insemination are important methods for giant panda breeding and preservation of extant genetic diversity. Lower conception rates limit the use of artificial insemination with frozen-thawed giant panda sperm, due to the lack of understanding of the cryodamaging or cryoinjuring mechanisms in cryopreservation. Long non-coding RNAs (lncRNAs) are involved in regulating spermatogenesis. However, their roles during cryopreservation remain largely unexplored. Therefore, this study aimed to identify differentially expressed lncRNAs and mRNAs associated with cryodamage or freeze tolerance in frozen-thawed sperm through high throughput sequencing. A total of 61.05 Gb clean reads and 22,774 lncRNA transcripts were obtained. From the sequencing results, 1477 significantly up-regulated and 1,396 significantly down-regulated lncRNA transcripts from fresh and frozen-thawed sperm of giant panda were identified. GO and KEGG showed that the significantly dysregulated lncRNAs and mRNAs were mainly involved in regulating responses to cold stress and apoptosis, such as the integral component of membrane, calcium transport, and various signaling pathways including PI3K-Akt, p53 and cAMP. Our work is the first systematic profiling of lncRNA and mRNA in fresh and frozen-thawed giant panda sperm, and provides valuableinsights into the potential mechanism of cryodamage in sperm.
Enhanced Pulsatile Growth Hormone Secretion and Altered Metabolic Hormones by in Vivo Hexarelin Treatment in Streptozotocin-Induced Diabetic Rats
Authors: Zhang Xinli , Yang Jin-Kui , Chen Chen
Published: October 2018

Significant growth hormone (GH) reductions have been reported in diabetic animal models with disturbed metabolic balance coinciding with GH deficiency. Therefore, enhanced GH secretion may have beneficial effects in controlling diabetes. Thus, we aim to investigate the effect of hexarelin, a synthetic GH secretagogue (GHS), on GH secretion in streptozotocin (STZ, 65 mg/kg)-induced diabetic rats. Daily hexarelin (100 μg/kg) treatment was performed for two weeks in four-week-long STZ-diabetic and vehicle control rats. Pulsatile GH secretion in STZ-rats was significantly reduced in total, pulsatile, basal, and mass of GH secretion per burst. In addition, impaired GH secretion was followed by an increase in fasting-level free fatty acids (FFAs) and a decrease in insulin-like growth factor 1 (IGF-1) compared to control rats. After hexarelin treatment, pulsatile GH secretion in STZ-rats was significantly increased in total, pulsatile, and basal, but not in the mass GH secretion per burst, compared to STZ-rats without hexarelin treatment. However, there was no significant elevation in GH secretion in the hexarelin-treated control group. In addition, hexarelin-treated STZ-rats showed a significant decrease in fasting level FFAs, whereas suppression of fasting level for IGF-1 was maintained. These results suggest that STZ-induced diabetic rats have impaired pulsatile GH secretion, causing increased FFAs and decreased IGF-1 levels in circulation. Hexarelin injections for two weeks is able to normalize impaired pulsatile GH secretion with normal fasting levels of FFAs, but fails to recover IGF-1 levels.
A Theory of Physically Embodied and Causally Effective Agency
Authors: Laskey Kathryn Blackmond
Published: October 2018

Causality is fundamental to agency. Intelligent agents learn about causal relationships by interacting with their environments and use their causal knowledge to choose actions intended to bring about desired outcomes. This paper considers a causal question that is central to the very meaning of agency, that of how a physically embodied agent effects intentional action in the world. The prevailing assumption is that both biological and computer agents are automatons whose decisions are determined by the physical processes operating in their information processing apparatus. As an alternative hypothesis, this paper presents a mathematical model of causally efficacious agency. The model is based on Stapp’s theory of efficacious choice in physically embodied agents. Stapp’s theory builds on a realistic interpretation of von Neumann’s mathematical formalization of quantum theory. Because it is consistent with the well-established precepts of quantum theory, Stapp’s theory has been dismissed as metaphysical and unfalsifiable. However, if taken seriously as a model of efficacious choice in biological agents, the theory does have empirically testable implications. This paper formulates Stapp’s theory as an interventionist causal theory in which interventions are ascribed to agents and can have macroscopically distinguishable effects in the world. Empirically testable implications of the theory are discussed and a path toward scientific evaluation is proposed. Implications for artificial intelligence are considered.
FBXL7 Upregulation Predicts a Poor Prognosis and Associates with a Possible Mechanism for Paclitaxel Resistance in Ovarian Cancer
Authors: Chiu Hui-Wen , Chang Jeng-Shou , Lin Hui-Yu , Lee Hsun-Hua , Kuei Chia-Hao , Lin Che-Hsuan , Huang Huei-Mei , Lin Yuan-Feng
Published: October 2018

Paclitaxel (PTX) is a common regimen used to treat patients with ovarian cancer. Although approximately 60% of ovarian cancer patients exhibit a pathologic complete response (pCR), approximately 40% of patients appear to be insensitive to PTX adjuvant therapy. Thus, identifying a useful biomarker to predict pCR would be of great help to ovarian cancer patients who decide to receive PTX treatment. We found that FBXL7 was downregulated in OVSAHO (PTX-sensitive) but upregulated in KURAMOCHI (PTX-resistant) cells after PTX treatment at cytotoxic concentrations. Moreover, our data showed that the fold change of FBXL7 expression post-treatment with PTX was causally correlated with the 50% inhibitory concentrations (IC50) of PTX in a panel of ovarian cancer cell lines. In assessments of progression-free survival probability, high levels of FBXL7 transcript strongly predicted a poor prognosis and unfavorable response to PTX-based chemotherapy in patients with ovarian cancer. The knockdown of FBXL7 predominantly enhanced the cytotoxic effectiveness of PTX on the PTX-resistant KURAMOCHI cells. FBXL7 may be a useful biomarker for predicting complete pathologic response in ovarian cancer patients who decide to receive post-operative PTX therapy.
Prescribing Hemodialysis or Hemodiafiltration: When One Size Does Not Fit All the Proposal of a Personalized Approach Based on Comorbidity and Nutritional Status
Authors: Piccoli Giorgina , Nielsen Louise , Gendrot Lurilyn , Fois Antioco , Cataldo Emanuela , Cabiddu Gianfranca
Published: October 2018

There is no simple way to prescribe hemodialysis. Changes in the dialysis population, improvements in dialysis techniques, and different attitudes towards the initiation of dialysis have influenced treatment goals and, consequently, dialysis prescription. However, in clinical practice prescription of dialysis still often follows a “one size fits all” rule, and there is no agreed distinction between treatment goals for the younger, lower-risk population, and for older, high comorbidity patients. In the younger dialysis population, efficiency is our main goal, as assessed by the demonstrated close relationship between depuration (tested by kinetic adequacy) and survival. In the ageing dialysis population, tolerance is probably a better objective: “good dialysis” should allow the patient to attain a stable metabolic balance with minimal dialysis-related morbidity. We would like therefore to open the discussion on a personalized approach to dialysis prescription, focused on efficiency in younger patients and on tolerance in older ones, based on life expectancy, comorbidity, residual kidney function, and nutritional status, with particular attention placed on elderly, high-comorbidity populations, such as the ones presently treated in most European centers. Prescription of dialysis includes reaching decisions on the following elements: dialysis modality (hemodialysis (HD) or hemodiafiltration (HDF)); type of membrane (permeability, surface); and the frequency and duration of sessions. Blood and dialysate flow, anticoagulation, and reinfusion (in HDF) are also briefly discussed. The approach described in this concept paper was developed considering the following items: nutritional markers and integrated scores (albumin, pre-albumin, cholesterol; body size, Body Mass Index (BMI), Malnutrition Inflammation Score (MIS), and Subjective Global Assessment (SGA)); life expectancy (age, comorbidity (Charlson Index), and dialysis vintage); kinetic goals (Kt/V, normalized protein catabolic rate (n-PCR), calcium phosphate, parathyroid hormone (PTH), beta-2 microglobulin); technical aspects including vascular access (fistula versus catheter, degree of functionality); residual kidney function and weight gain; and dialysis tolerance (intradialytic hypotension, post-dialysis fatigue, and subjective evaluation of the effect of dialysis on quality of life). In the era of personalized medicine, we hope the approach described in this concept paper, which requires validation but has the merit of providing innovation, may be a first step towards raising attention on this issue and will be of help in guiding dialysis choices that exploit the extraordinary potential of the present dialysis “menu”.
The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Critically Ill Patients
Authors: Park Ji Eun , Chung Kyung Soo , Song Joo Han , Kim Song Yee , Kim Eun Young , Jung Ji Ye , Kang Young Ae , Park Moo Suk , Kim Young Sam , Chang Joon , Leem Ah Young
Published: October 2018

The C-reactive protein (CRP)/albumin ratio has recently emerged as a marker for poor prognosis or mortality across various patient groups. This study aimed to identify the association between CRP/albumin ratio and 28-day mortality and predict the accuracy of CRP/albumin ratio for 28-day mortality in medical intensive care unit (ICU) patients. This was a retrospective cohort study of 875 patients. We evaluated the prognostic value of CRP/albumin ratio to predict mortality at 28 days after ICU admission, using Cox proportional hazard model and Kaplan-Meier survival analysis. The 28-day mortality was 28.0%. In the univariate analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p < 0.001), CRP level (p = 0.045), albumin level (p < 0.001), and CRP/albumin ratio (p = 0.032) were related to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (the area under the ROC curves (AUC)) of CRP/albumin ratio was higher than that of CRP for mortality (0.594 vs. 0.567, p < 0.001). The cut-off point for CRP/albumin ratio for mortality was 34.3. On Cox proportional-hazard regression analysis, APACHE II score (hazards ratio (HR) = 1.05, 95% confidence interval (CI) = 1.04–1.07, p < 0.001) and CRP/albumin ratio (HR = 1.68, 95% CI = 1.27–2.21, p < 0.001 for high CRP/albumin ratio) were independent predictors of 28-day mortality. Higher CRP/albumin ratio was associated with increased mortality in critically ill patients.
Longitudinal IQ Trends in Children Diagnosed with Emotional Disturbance: An Analysis of Historical Data
Authors: Kanaya Tomoe , Ceci Stephen J.
Published: October 2018

The overwhelming majority of the research on the historical impact of IQ in special education has focused on children with cognitive disorders. Far less is known about its role for students with emotional concerns, including Emotional Disturbance (ED). To address this gap, the current study examined IQ trends in ED children who were repeatedly tested on various combinations of the WISC, WISC-R, and WISC-III using a geographically diverse, longitudinal database of special education evaluation records. Findings on test/re-test data revealed that ED children experienced IQ trends that were consistent with previous research on the Flynn effect in the general population. Unlike findings associated with test/re-test data for children diagnosed with cognitive disorders, however, ED re-diagnoses were unaffected by these trends. Specifically, ED children’s declining IQ scores when retested on newer norms did not result in changes in their ED diagnosis. The implications of this unexpected finding are discussed within the broader context of intelligence testing and special education policies.
Compatibility of a Silicone Impression/Adhesive System to FDM-Printed Tray Materials—A Laboratory Peel-off Study
Authors: Xu Yichen , Unkovskiy Alexey , Klaue Felix , Rupp Frank , Geis-Gerstorfer Juergen , Spintzyk Sebastian
Published: October 2018

Computer-aided design (CAD) and additive manufacturing (AM) have shown promise in facilitating the fabrication of custom trays. Due to the clinical requirements, custom tray materials should achieve good bonding to the impression/adhesive systems. This study evaluated the retention of three fused deposition modeling (FDM) custom tray materials to a silicone impression/adhesive system before and after gritblasting (GB) by peel-off test. CAD-designed experimental test blocks were printed by FDM using acrylonitrile butadiene styrene (ABS), polyethylene terephthalate glycol copolyester (PETG), and high impact polystyrene (HIPS), and the reference test blocks were made of a conventional light-curing resin (n = 11). Before and after GB, the surface topography of all tray materials was analysed, and the maximum strength of the test block peeled off from a silicone impression/adhesive system was measured. After GB, the arithmetic mean height (Sa) and the valley fluid retention index (Svi) of the four material groups declined (p < 0.05). The peel-off strength of each of the four material groups significantly decreased by GB (p < 0.05), but no statistical difference could be found among them before or after GB. In all peel-off tests, adhesive failure occurred at the adhesive-impression material interface. The results indicated ABS, HIPS, and PETG could provide sufficient adhesion to the adhesive as the conventional light-curing resin, and GB could reduce the roughness generated by FDM and weaken the bonding between the adhesive and the silicone impression.
Effects of Laser Welding and Post-Weld Heat Treatment on Microstructure and Mechanical Properties of Aged Ti55531 Alloy
Authors: Zhang Lin-Jie , Pei Jun-Yu , Long Jian , Xie Miao-Xia , Shang Xiang-Tao , Wu Jun
Published: October 2018

As one of the relatively new titanium (Ti) alloys in the engineering field, β-Ti alloy–Ti55531 has attracted a great deal of attention due to its excellent mechanical properties, while a few research papers on weldability and the post-weld heat treatment (PWHT) process of Ti55531 have been reported. Based on an orthogonal experiment design, the parameters of laser beam welding (LBW) of Ti55531 alloy with a thickness of 2 mm were optimized. Moreover, the influences of welding parameters and PWHT on the microstructures and performance of the laser-welded joint of Ti55531 were analyzed. The results showed that, for microstructures in different zones of as-welded joints of Ti55531: three forms of α phases (i.e., equiaxial αp phase, lamellar αS phase, and αGB phase at grain boundaries) were observed in base metal (BM); in the heat affected zone (HAZ), part of lamellar αS phase had dissolved while equiaxial αp phase had grown; the fusion zone (FZ) mainly consisted of β phase, which presented as coarse columnar crystals. After the PWHT process, the microstructures of the welded joint were changed: in the BM zone, α phase at grain boundary disappeared and lamellar α phase decreased; in the HAZ, the edge of αp phase obviously dissolved; in the FZ, plenty of compact needle-like α phases were observed. The tensile strength of the as-welded joint was about 940 MPa and then increased to 1161 MPa after PWHT, which were 78.4% and 96.8% of that of the original BM respectively. The fracture position transformed from the interface between the FZ and HAZ to the BM during tensile tests after PWHT.
Microdialysis-Assessed Adipose Tissue Metabolism, Circulating Cytokines and Outcome in Critical Illness
Authors: Ilias Ioannis , Apollonatou Sofia , Nikitas Nikitas , Theodorakopoulou Maria , Vassiliou Alice G , Kotanidou Anastasia , Dimopoulou Ioanna
Published: October 2018

Microdialysis (MD) can provide continuous information about tissue composition. To assess in critically ill patients adipose tissue metabolic patterns, the relationships between metabolic patterns and blood cytokine concentration associations of adipose tissue energy metabolism and clinical outcome we studied 203 mechanically ventilated general intensive care unit (ICU) patients. Upon ICU admission an MD catheter was inserted into the subcutaneous adipose tissue of the upper thigh to measure lactate (L), glucose, pyruvate (P), and glycerol. Serum concentrations of IL-10, IL-6, IL-8, and TNF-α were determined within 48 h from ICU admission. Mitochondrial dysfunction was defined as L/P ratio >30 and pyruvate ≥70 μmol/L, ischemia as L/P ratio >30 and pyruvate <70 μmol/L and no ischemia/no mitochondrial dysfunction (i.e., aerobic metabolism) was as L/P ratio ≤30. Metabolism was aerobic in 74% of patients. In 13% of patients there was biochemical evidence of ischemia and in 13% of patients of mitochondrial dysfunction. Mitochondrial dysfunction was associated with poor outcome. In conclusion, MD showed that about two thirds of critically ill patients have normal aerobic adipose tissue metabolism. Mitochondrial dysfunction was not common but was associated with poor outcome. Identifying subgroups of critically ill patients is crucial as different treatment strategies may improve survival.
The Hajjar Regional Transpressive Shear Zone (Guemassa Massif, Morocco): Consequences on the Deformation of the Base-Metal Massive Sulfide Ore
Authors: Admou Safouane , Branquet Yannick , Badra Lakhlifi , Barbanson Luc , Outhounjite Mohamed , Khalifa Abdelali , Zouhair Mohamed , Maacha Lhou
Published: October 2018

The genesis of the base-metal massive sulfide deposits hosted within the Moroccan Hercynian Jebilet and Guemassa Massifs is still under debate. No consensus currently exists between the two models that have been proposed to explain the deposits, i.e., (1) syngenetic volcanogenic massive sulfide mineralization, and (2) synmetamorphic tectonic fluid-assisted epigenetic mineralization. Conversely, researchers agree that all Hercynian massive sulfide deposits in Morocco are deformed, even though 3D structural mapping at the deposit scale is still lacking. Therefore, while avoiding the use of a model-driven approach, the main aim of this contribution is to establish a first-order structural pattern and the controls of the Hajjar base metal deposit. We used a classical structural geology toolbox in surface and subsurface mining work to image finite strain at different levels. Our data demonstrate that: i) the Hajjar area is affected by a single foliation plane (not two) which developed during a single tectonic event encompassing a HT metamorphism. This syn-metamorphic deformation is not restricted to the Hajjar area, as it is widespread at the western Meseta scale, and it occurred during Late Carboniferous times; ii) the Hajjar ore deposit is hosted within a regional transpressive right-lateral NE-trending shear zone in which syn- to post-metamorphic ductile to brittle shear planes are responsible for significant inflexion (or virgation) of the foliation yielding an anastomosing pattern within the Hajjar shear zone. Again, this feature is not an exception, as various Late Carboniferous-Permian regional scale wrenching shear zones are recognized throughout the Hercynian Meseta orogenic segment. Finally, we present several lines of evidence emphasizing the role of deformation in terms of mechanical and fluid-assisted ore concentrations.
Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid Didymin
Authors: Yao Qing , Lin Meng-Ting , Zhu Yin-Di , Xu He-Lin , Zhao Ying-Zheng
Published: October 2018

Didymin (isosakuranetin 7-O-rutinoside) is an orally bioactive dietary flavonoid glycoside first found in citrus fruits. Traditionally, this flavonoid has long been used in Asian countries as a dietary antioxidant. Recent studies have provided newer insights into this pleiotropic compound, which could regulate multiple biological activities of many important signaling molecules in health and disease. Emerging data also presented the potential therapeutic application of dietary flavonoid glycoside didymin against cancer, neurological diseases, liver diseases, cardiovascular diseases, and other diseases. In this review, we briefly introduce the source and extraction methods of didymin, and summarize its potential therapeutic application in the treatment of various diseases, with an emphasis on molecular targets and mechanism that contributes to the observed therapeutic effects. The dietary flavonoid didymin can be used to affect health and disease with multiple therapeutic targets, and it is anticipated that this review will stimulate the future development of this potential dietary medicine.
Ethylenediamine Derived Carboxamides of Betulinic and Ursolic Acid as Potential Cytotoxic Agents
Authors: Kahnt Michael , Fischer (née Heller) Lucie , Al-Harrasi Ahmed , Csuk René
Published: October 2018

Two easily accessible, natural occurring triterpenoids, betulinic and ursolic acid, were used as starting materials for the synthesis of novel cytotoxic agents. A set of 28 ethylenediamine-spacered carboxamides was prepared holding an additional substituent connected to the ethylenediamine group. The compounds were screened in SRB assays to evaluate their cytotoxic activity employing several human tumor cell lines. Betulinic acid-derived carboxamides 17–30 showed significantly higher cytotoxicity than their ursolic acid analogs 3–16. In particular, compounds 25 and 26 were highly cytotoxic, as indicated by EC50 values lower than 1 μM.
Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides
Authors: Wang Tao , Larcher Leon M. , Ma Lixia , Veedu Rakesh N.
Published: October 2018

Non-viral vector-mediated transfection is a core technique for in vitro screening of oligonucleotides. Despite the growing interests in the development of oliogonucleotide-based drug molecules in recent years, a comprehensive comparison of the transfection efficacy of commonly used commercial transfection reagents has not been reported. In this study, five commonly used transfection reagents, including Lipofectamine 3000, Lipofectamine 2000, Fugene, RNAiMAX and Lipofectin, were comprehensively analyzed in ten cell lines using a fluorescence imaging-based transfection assay. Although the transfection efficacy and toxicity of transfection reagents varied depending on cell types, the toxicity of transfection reagents generally displayed a positive correlation with their transfection efficacy. According to our results, Lipofectamine 3000, Fugene and RNAiMAX showed high transfection efficacy, however, RNAiMAX may be a better option for majority of cells when lower toxicity is desired. The transfection efficacy of Lipofectamine 2000 was compromised by its high toxicity, which may adversely affect its application in most cells. We firmly believe that our findings may contribute to the future In vitro delivery and screening of single-stranded therapeutic oligonucleotides such as antisense oligonucleotides, antimiRs, and DNAzymes.
Chemical Components and Biological Activities of the Genus Phyllanthus: A Review of the Recent Literature
Authors: Nisar Muhammad Farrukh , He Junwei , Ahmed Arsalan , Yang Youxin , Li Mingxi , Wan Chunpeng
Published: October 2018

Medicinal plants have served humans since prehistoric times to treat various ailments. Both developed and underdeveloped countries rely on traditional systems of medication using natural sources from plants. Phyllanthus is one of the largest genus in the family Phyllanthaceae, comprising over 700 well known species cosmopolitan in distribution mainly in the tropics and subtropics. Phyllanthus species are being in constant used in traditional medications to cure an array of human diseases (constipation, inhalation related, arthritis, loss of appetite, injuries, conjunctivitis, diarrhoea, running nose, common cold, malaria, blennorrhagia, colic, diabetes mellitus, dysentery, indigestion, fever, gout, gonorrheal diseases of males and females, skin itching, jaundice, hepatic disorders, leucorrhea, vaginitis, menstrual irregularities, obesity, stomach pains, and tumors), confectionaries, food industry, and in some pesticides. Phyllanthus species are rich in diversity of phytochemicals e.g., tannins, terpenes, alkaloids, glycosidic compounds, saponins, and flavones etc. More in depth studies are a direly needed to identify more compounds with specific cellular functions to treat various ailments.
The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial Cells
Authors: Park Yong Joo , Lee Seoung Rak , Kim Dong Min , Yu Jae Sik , Beemelmanns Christine , Chung Kyu Hyuck , Kim Ki Hyun
Published: October 2018

Pulmonary fibrosis (PF) is a chronic and fatal lung disease with few treatment options. Although the pathogenesis of PF is not clear, a chronic inflammatory response to continuous damage is considered the cause of pulmonary fibrosis. PF is characterized by excessive accumulation of extracellular matrix (ECM), therefore, inhibition of myofibroblast differentiation is a good therapeutic target for PF. As part of our continuing endeavor to explore biologically active metabolites from insect-associated microbes, we found that the MeOH extract of the culture broth from the entomopathogenic fungus Beauveria bassiana inhibited collagen induction and E-cadherin down-regulation. In order to identify active compounds, we carried out chemical analysis of the MeOH extract with the assistance of LC/MS-guided isolation approach, which led to the successful identification of four cyclodepsipeptides 1–4. Among the isolates, compound 2 showed inhibitory effects on myofibroblast differentiation induced by TGF-β1. Compound 2 inhibited induction of α-SMA and N-cadherin, which are myofibroblast markers, and blocked the accumulation of ECM proteins such as collagen and fibronectin. Overall these findings demonstrate that compound 2 can be used to attenuate pulmonary fibrosis by targeting myo- fibroblast differentiation.
Nb2O5 and Ti-Doped Nb2O5 Charge Trapping Nano-Layers Applied in Flash Memory
Authors: Wang Jer Chyi , Kao Chyuan Haur , Wu Chien Hung , Lin Chun Fu , Lin Chih Ju
Published: October 2018

High-k material charge trapping nano-layers in flash memory applications have faster program/erase speeds and better data retention because of larger conduction band offsets and higher dielectric constants. In addition, Ti-doped high-k materials can improve memory device performance, such as leakage current reduction, k-value enhancement, and breakdown voltage increase. In this study, the structural and electrical properties of different annealing temperatures on the Nb2O5 and Ti-doped Nb2O5(TiNb2O7) materials used as charge-trapping nano-layers in metal-oxide-high k-oxide-semiconductor (MOHOS)-type memory were investigated using X-ray diffraction (XRD) and atomic force microscopy (AFM). Analysis of the C-V hysteresis curve shows that the flat-band shift (∆VFB) window of the TiNb2O7 charge-trapping nano-layer in a memory device can reach as high as 6.06 V. The larger memory window of the TiNb2O7 nano-layer is because of a better electrical and structural performance, compared to the Nb2O5 nano-layer.
Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model–Part II: Microglia and Mitochondria
Authors: Hayden Melvin , Grant DeAna , Aroor Annayya , DeMarco Vincent
Published: October 2018

Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. This study tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions may depict abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks), left-brain hemispheres of the DBC and age-matched nondiabetic control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We observed an attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickened basement membranes, adherent red and white blood cells, neurovascular unit microbleeds and pathologic remodeling of protoplasmic astrocytes. In this second of a three-part series, we focus on the observational ultrastructural remodeling of microglia and mitochondria in relation to the NVU in leptin receptor deficient DBC models. This study identified novel ultrastructural core signature remodeling changes, which consisted of invasive activated microglia, microglial aberrant mitochondria with nuclear chromatin condensation and adhesion of white blood cells to an activated endothelium of the NVU. In conclusion, the results implicate activated microglia in NVU uncoupling and the resulting ischemic neuronal and synaptic damage, which may be related to impaired cognition and diabetic cognopathy.
Fabrication and Characterization of Strontium-Substituted Hydroxyapatite-CaO-CaCO3 Nanofibers with a Mesoporous Structure as Drug Delivery Carriers
Authors: Tsai Shiao-Wen , Yu Wen-Xin , Hwang Pai-An , Huang Sheng-Siang , Lin Hsiu-Mei , Hsu Yu-Wei , Hsu Fu-Yin
Published: October 2018

Hydroxyapatite (HAp) is the main inorganic component and an essential part of hard bone and teeth. Due to its excellent biocompatibility, bioactivity, and osteoconductivity, synthetic HAp has been widely used as a bone substitute, cell carrier, and therapeutic gene or drug carrier. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHAp) not only enhances osteogenesis but also inhibits adipogenesis in mesenchymal stem cells. Mesoporous SrHAp has been successfully synthesized via a traditional template-based process and has been found to possess better drug loading and release efficiencies than SrHAp. In this study, strontium-substituted hydroxyapatite-CaO-CaCO3 nanofibers with a mesoporous structure (mSrHANFs) were fabricated using a sol–gel method followed by electrospinning. X-ray diffraction analysis revealed that the contents of CaO and CaCO3 in the mSrHANFs decreased as the doping amount of Sr increased. Scanning electron microscopy (SEM) images showed that the average diameter of the mSrHANFs was approximately 200~300 nm. The N2 adsorption–desorption isotherms demonstrated that the mSrHANFs possessed a mesoporous structure and that the average pore size was approximately 20~25 nm. Moreover, the mSrHANFs had excellent drug- loading efficiency and could retard the burst release of tetracycline (TC) to maintain antibacterial activity for over 3 weeks. Hence, mSrHANFs have the potential to be used as drug carriers in bone tissue engineering.
Effect of Morphological Changes due to Increasing Carbon Nanoparticles Content on the Quasi-Static Mechanical Response of Epoxy Resin
Authors: Nezhad Hamed Yazdani , Thakur Vijay Kumar
Published: October 2018

Mechanical failure in epoxy polymer and composites leads them to commonly be referred to as inherently brittle due to the presence of polymerization-induced microcrack and microvoids, which are barriers to high-performance applications, e.g., in aerospace structures. Numerous studies have been carried out on epoxy’s strengthening and toughening via nanomaterial reinforcement, e.g., using rubber nanoparticles in the epoxy matrix of new composite aircraft. However, extremely cautious process and functionalization steps must be taken in order to achieve high-quality dispersion and bonding, the development of which is not keeping pace with large structures applications. In this article, we report our studies on the mechanical performance of an epoxy polymer reinforced with graphite carbon nanoparticles (CNPs), and the possible effects arising from a straightforward, rapid stir-mixing technique. The CNPs were embedded in a low viscosity epoxy resin, with the CNP weight percentage (wt %) being varied between 1% and 5%. Simplified stirring embedment was selected in the interests of industrial process facilitation, and functionalization was avoided to reduce the number of parameters involved in the study. Embedment conditions and timing were held constant for all wt %. The CNP filled epoxy resin was then injected into an aluminum mold and cured under vacuum conditions at 80 °C for 12 h. A series of test specimens were then extracted from the mold, and tested under uniaxial quasi-static tension, compression, and nanoindentation. Elementary mechanical properties including failure strain, hardness, strength, and modulus were measured. The mechanical performance was improved by the incorporation of 1 and 2 wt % of CNP but was degraded by 5 wt % CNP, mainly attributed to the morphological change, including re-agglomeration, with the increasing CNP wt %. This change strongly correlated with the mechanical response in the presence of CNP, and was the major governing mechanism leading to both mechanical improvement and degradation.
One-Step Quaternization/Hydroxypropylsulfonation to Improve Paste Stability, Adhesion, and Film Properties of Oxidized Starch
Authors: Li Wei , Xu Zhenzhen , Wang Zongqian , Xing Jian
Published: October 2018

To investigate the influences of quaternization/hydroxypropylsulfonation on viscosity stability, adhesion to fibers and film properties of oxidized tapioca starch (OTS) for ameliorating its end-use ability in applications such as warp-sizing and paper-making, a series of quaternized and hydroxypropylsulfonated OTS (QHOTS) samples were synthesized by simultaneous quaternization and hydroxypropylsulfonation of OTS with N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride (CHPTAC) and 3-chloro-2-hydroxy-1-propanesulfonic acid sodium salt (CHPS-Na). The QHOTS granules were characterized by Fourier transform infra-red spectroscopic and scanning electron microscope techniques. Apparent viscosity and viscosity stability were determined, and adhesion was evaluated by measuring the bonding force of starch to the fibers. Film properties were also estimated in terms of tensile strength, breaking elongation, bending endurance, degree of crystallinity, and moisture regain. It was showed that quaternization/hydroxypropylsulfonation was capable of obviously improving viscosity stability of gelatinized OTS paste, enhancing bonding forces of OTS to cotton and polylactic acid (PLA) fibers, increasing breaking elongation, bending endurance and moisture regain of film and decreasing its tensile strength and degree of crystallinity, thereby obviously stabilizing paste viscosity, improving adhesion to fibers and lessening film brittleness. Increasing the level of quaternization/hydroxypropylsulfonation favored improvement in the stability, enhancement in adhesion and decrease in brittleness. The QHOTS showed potential in the applications of cotton and PLA sizing.