bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle
Authors: López-Canul Martha , Min Seung Hyun , Posa Luca , De Gregorio Danilo , Bedini Annalida , Spadoni Gilberto , Gobbi Gabriella , Comai Stefano
Published: May 2019

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.
Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer
Authors: Ismail Nor Isnida , Othman Iekhsan , Abas Faridah , H. Lajis Nordin , Naidu Rakesh
Published: May 2019

Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.
Therapeutic Potential of Iridoid Derivatives: Patent Review
Authors: Hussain Hidayat , Green Ivan R. , Saleem Muhammad , Raza Muhammad Liaquat , Nazir Mamona
Published: May 2019

Iridoids belong to a family of monoterpenoids comprising the cyclopentan[c]-pyran system; this class of compounds offers a wide range of biological effects, namely antileishmanial, anticancer, antiplasmodial, and anti-inflammatory potency. To date, a large number of biologically active iridoid derivatives have been reported from various plant families, including Rubiaceae, Plantaginaceae, Scrophulariaceae, and Verbenaceae. Furthermore, iridoids have the potential to form conjugates with other anticancer, antidiabetic, antileishmanial, and antimalarial drugs which synergistically have the potential to increase their effects. Additionally, future research should focus on the synthesis of halo analogs as well as preparing homo dimers or heterodimers of iridoids, since these might quite conceivably possess an increased bioactivity.
Use of Complementary and Alternative Medicine in Axial Spondyloarthritis: A Qualitative Exploration of Self-Management
Authors: Jordan Abbie , Family Hannah , Blaxall Kelly , Begen Fiona M. , Sengupta Raj
Published: May 2019

Axial spondyloarthritis (axSpA) is an inflammatory rheumatic condition that is often subject to diagnostic delays. Individuals with axSpA report using complementary and alternative therapies prior to and following diagnosis, though little is known concerning reasons underlying use of such therapies. This study provides detailed insights into the motivation and experiences of complementary and alternative medicine use within a population of individuals with axSpA. Open-ended surveys were completed by 30 individuals (20–69 years; 17 females) diagnosed with axSpA. Subsequent telephone interviews were conducted with eight individuals (39–70 years; five females) diagnosed with axSpA. Data were analyzed using reflexive inductive thematic analysis. Themes of “a learning curve”, “barriers to complementary and alternative therapy use” and “complementary or mutually exclusive” illustrated how participants” increasing understanding of their condition empowered them to explore complementary and alternative therapies use as an adjunct to mainstream care. Individuals with axSpA recommended greater integration between mainstream and complementary and alternative therapies, valuing informed advice from mainstream healthcare professionals before selecting appropriate complementary and alternative therapies for potential use. Healthcare professionals should be proactive in discussing complementary and alternative therapy use with patients and supply them with details of organizations that can provide good-quality information.
Factors for the Early Revision of Misdiagnosed Tuberculosis to Lung Cancer: A Multicenter Study in A Tuberculosis-Prevalent Area
Authors: Shu Chin-Chung , Chang Shih-Chieh , Lai Yi-Chun , Chang Cheng-Yu , Wei Yu-Feng , Chen Chung-Yu
Published: May 2019

Background: Lung cancer misdiagnosed as tuberculosis (TB) is not rare, but the factors associated with early diagnosis revision remain unclear. Methods: We screened the cases with TB notification from 2007 to 2018 and reviewed those with misdiagnosis with a revised diagnosis to lung cancer. We analyzed the factors associated with early diagnosis revision (≤1 months) and early obtained pathology (≤1 months) using multivariable Cox regression. Results: During the study period, 45 (0.7%) of 6683 patients were initially notified as having TB, but later diagnosed with lung cancer. The reasons for the original impression of TB were mostly due to image suspicion (51%) and positive sputum acid-fast stain (AFS) (27%). Using multivariable Cox proportional regression, early diagnosis revision was associated with obtaining the pathology early, lack of anti-TB treatment, and negative sputum AFS. Furthermore, the predictors for early obtained pathology included large lesion size (>3 cm), presence of a miliary radiological pattern, no anti-TB treatment, and a culture-negative result when testing for nontuberculous mycobacteria (NTM) using multivariable Cox regression. Conclusion: In patients who are suspected to have TB but no mycobacterial evidence is present, lung cancer should be kept in mind and pathology needs to be obtained early, especially for those with small lesions, radiological findings other than the miliary pattern, and a culture positive for NTM.
Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks
Authors: Tsai Kelvin K. , Chan Tze-Sian , Shaked Yuval
Published: May 2019

Pancreatic ductal adenocarcinoma (PDAC) is a devastating and highly aggressive malignancy. Existing therapeutic strategies only provide a small survival benefit in patients with PDAC. Laboratory and clinical research have identified various populations of stem-cell-like cancer cells or cancer stem cells (CSCs) as the driving force of PDAC progression, treatment-resistance, and metastasis. Whilst a number of therapeutics aiming at inhibiting or killing CSCs have been developed over the past decade, a series of notable clinical trial setbacks have led to their deprioritization from the pipelines, triggering efforts to refine the current CSC model and exploit alternative therapeutic strategies. This review describes the current and the evolving models of pancreatic CSCs (panCSCs) and the potential factors that hamper the clinical development of panCSC-targeted therapies, emphasizing the heterogeneity, the plasticity, and the non-binary pattern of cancer stemness, as well as the desmoplastic stroma impeding drug penetration. We summarized novel and promising therapeutic strategies implicated by the works of our groups and others’ that may overcome these hurdles and have shown efficacies in preclinical models of PDAC, emphasizing the unique advantages of targeting the stroma-engendered panCSC-niches and metronomic chemotherapy. Finally, we proposed feasible clinical trial strategies and biomarkers that can guide the next-generation clinical trials.
(Don’t) Look at Me! How the Assumed Consensual or Non-Consensual Distribution Affects Perception and Evaluation of Sexting Images
Authors: Dekker Arne , Wenzlaff Frederike , Daubmann Anne , Pinnschmidt Hans O. , Briken Peer
Published: May 2019

The non-consensual sharing of an intimate image is a serious breach of a person’s right to privacy and can lead to severe psychosocial consequences. However, little research has been conducted on the reasons for consuming intimate pictures that have been shared non-consensually. This study aims to investigate how the supposed consensual or non-consensual distribution of sexting images affects the perception and evaluation of these images. Participants were randomly assigned to one of two groups. The same intimate images were shown to all participants. However, one group assumed that the photos were shared voluntarily, whereas the other group were told that the photos were distributed non-consensually. While the participants completed several tasks such as rating the sexual attractiveness of the depicted person, their eye-movements were being tracked. The results from this study show that viewing behavior and the evaluation of sexting images are influenced by the supposed way of distribution. In line with objectification theory men who assumed that the pictures were distributed non-consensually spent more time looking at the body of the depicted person. This so-called ‘objectifying gaze’ was also more pronounced in participants with higher tendencies to accept myths about sexual aggression or general tendencies to objectify others. In conclusion, these results suggest that prevention campaigns promoting ‘sexting abstinence’ and thus attributing responsibility for non-consensual distribution of such images to the depicted persons are insufficient. Rather, it is necessary to emphasize the illegitimacy of the non-consensual distribution of sexting images, especially among male consumers of the material.
Comparison between Surgical and Conservative Treatment for Distal Radius Fractures in Patients over 65 Years
Authors: Testa Gianluca , Vescio Andrea , Di Masi Paola , Bruno Giulio , Sessa Giuseppe , Pavone Vito
Published: May 2019

Background: Fractures of the distal radius (DRF) are the most common orthopedic injuries, representing one of the typical fractures indicating underlying osteoporosis. The aim of the study was to compare conservative and surgical treatment, analyzing quality of life and clinical outcome in an over 65 years old population. Methods: Ninety one patients were divided into two groups: the ORIF group (39 patients) underwent surgery, and the conservative group (52 patients) was treated conservatively. The clinical and functional outcomes of all patients were evaluated using Short Form 36 (SF36), Modified Mayo Wrist Score (MMWS), Disability of the Arm Shoulder Hand (DASH), and Visual Analogue Scale (VAS). Range of motion at the joint was measured and compared with the contralateral healthy wrist. Results: No significant difference was found between the overall SF36 score, DASH score, MMWS, and VAS results. Role limitation was significantly better in the surgical group (p < 0.05), and complication incidence was significantly higher (p < 0.05) in the conservative group. Conclusion: The results of this study conform to recent literature, suggesting that a surgical reconstruction of the radius articular surface in an elderly population provides no clear clinical advantage. Treatment decisions must arise from careful diagnoses of the fracture and communication with the patient.
Design and Experiment of Clamper Used in Antarctic Subglacial Bedrock Drilling
Authors: Talalay Pavel , Li Xingchen , Gong Da , Fan Xiaopeng , Zhang Nan , Yang Yang , Liu Yongwen , Liu Yunchen , Wang Ting , Li Xiao
Published: May 2019

As a result of the severe natural environment with oxygen deficit in the Antarctic, using conventional manual work to screw and unscrew the drill pipe increases the labor intensity tremendously and causes an efficiency reduction. Therefore, it would be useful to design a clamper inside the drilling shelter, which could help to assemble and disassemble the ice core barrel with screw connection. This paper describes the design of and experiments with the clamper inside the movable drilling shelter. A related testing stand was also designed and built to experiment on relationships between the clamper motor current versus clamping torque and force. Through experimental data collation and calculation analysis, the following conclusions could be drawn: (1) according to the rotary ability of the Ice and Bedrock Electromechanical Drill (IBED) to calculate and determine the torque of clamper, the clamping torque required to provide by the clamper is 100 N·m; (2) finite element simulation and analysis of the non-standard transmission chain showed that the mechanical reliability of the subparts; (3) the experimental results showed the range of the clamping force and clamping torque of the clamper. The clamping force and clamping torque increased with the increase of clamper DC motor current, presenting proportional linear relationships. The clamper can meet the clamping requirements of IBED for screwing, unscrewing, and clamping, which will be greatly helpful when it is tested in the field.
Parametric Study of Tsunamis Generated by Earthquakes and Landslides
Authors: Perez del Postigo Prieto Natalia , Raby Alison , Whittaker Colin , Boulton Sarah J.
Published: May 2019

Tsunami generation and propagation mechanisms need to be clearly understood in order to inform predictive models and improve coastal community preparedness. Physical experiments, supported by mathematical models, can potentially provide valuable input data for standard predictive models of tsunami generation and propagation. A unique experimental set-up has been developed to reproduce a coupled-source tsunami generation mechanism: a two-dimensional underwater fault rupture followed by a submarine landslide. The test rig was located in a 20 m flume in the COAST laboratory at the University of Plymouth. The aim of the experiments is to provide quality data for developing a parametrisation of the initial conditions for tsunami generation processes which are triggered by a dual-source. During the test programme, the water depth and the landslide density were varied. The position of the landslide model was tracked and the free surface elevation of the water body was measured. Hence the generated wave characteristics were determined. For a coupled-source scenario, the generated wave is crest led, followed by a trough of smaller amplitude decreasing steadily as it propagates along the flume. The crest amplitude was shown to be influenced by the fault rupture displacement scale, whereas the trough was influenced by the landslide’s relative density.
Possibilities of Dry and Lubricated Friction Modification Enabled by Different Ultrashort Laser-Based Surface Structuring Methods
Authors: Rung Stefan , Bokan Kevin , Kleinwort Frederick , Schwarz Simon , Simon Peter , Klein-Wiele Jan-Hendrik , Esen Cemal , Hellmann Ralf
Published: May 2019

In this contribution we report on the possibilities of dry and lubricated friction modification introduced by different laser surface texturing methods. We compare the potential of Laser-Induced Periodic Surface Structures and Laser Beam Interference Ablation on 100Cr6 steel in a linear reciprocating ball-on-disc configuration using 100Cr6 steel and tungsten carbide balls with load forces between 50 mN and 1000 mN. For dry friction, we find a possibility to reduce the coefficient of friction and we observe a pronounced direction dependency for surfaces fabricated by Laser Beam Interference Ablation. Furthermore, Laser-Induced Periodic Surface Structures result in a load-dependent friction reduction for lubricated linear reciprocating movements. This work helps to identify the modification behaviour of laser generated micro structures with feature sizes of approximately 1 µm and reveals new possibilities for surface engineering.
4b,5,6,9-Tetrahydro-7H-dibenzo[c,e]pyrrolo[1,2-a]azepin-7-one
Authors: Boichenko Maksim A. , Babkin Igor Yu. , Kobylskoy Sergey G. , Chagarovskiy Alexey O. , Ivanova Olga A. , Trushkov Igor V.
Published: May 2019

A simple approach to synthesize 4b,5,6,9-tetrahydro-7H-dibenzo[c,e]pyrrolo[1,2-a]azepin- 7-one has been developed, based on a three-step transformation of 2-(2-bromophenyl)cyclopropane-1,1-diester. The key stage in this method is an intramolecular cross-coupling of 1-(2-bromobenzyl)-5-(2-bromophenyl)pyrrolidin-2-one under continuous flow conditions in an H-Сube-Pro using commercially available supported Pd catalysts.
Hermite-Hadamard Type Inequalities for Interval (h1, h2)-Convex Functions
Authors: An Yanrong , Ye Guoju , Zhao Dafang , Liu Wei
Published: May 2019

We introduce the concept of interval ( h 1 , h 2 ) -convex functions. Under the new concept, we establish some new interval Hermite-Hadamard type inequalities, which generalize those in the literature. Also, we give some interesting examples.
Positive Solutions for a Hadamard Fractional p-Laplacian Three-Point Boundary Value Problem
Authors: Jiang Jiqiang , O’Regan Donal , Xu Jiafa , Cui Yujun
Published: May 2019

This article is to study a three-point boundary value problem of Hadamard fractional p-Laplacian differential equation. When our nonlinearity grows ( p − 1 ) -superlinearly and ( p − 1 ) -sublinearly, the existence of positive solutions is obtained via fixed point index. Moreover, using an increasing operator fixed-point theorem, the uniqueness of positive solutions and uniform convergence sequences are also established.
On (Λ,Υ,ℜ)-Contractions and Applications to Nonlinear Matrix Equations
Authors: Ameer Eskandar , Nazam Muhammad , Aydi Hassen , Arshad Muhammad , Mlaiki Nabil
Published: May 2019

In this paper, we study the behavior of Λ , Υ , ℜ -contraction mappings under the effect of comparison functions and an arbitrary binary relation. We establish related common fixed point theorems. We explain the significance of our main theorem through examples and an application to a solution for the following nonlinear matrix equations: X = D + ∑ i = 1 n A i ∗ X A i − ∑ i = 1 n B i ∗ X B i X = D + ∑ i = 1 n A i ∗ γ X A i , where D is an Hermitian positive definite matrix, A i , B i are arbitrary p × p matrices and γ : H ( p ) → P ( p ) is an order preserving continuous map such that γ ( 0 ) = 0 . A numerical example is also presented to illustrate the theoretical findings.
Biochemical Markers of Renal Hypoperfusion, Hemoconcentration, and Proteinuria after Extreme Physical Exercise
Authors: Wołyniec Wojciech , Kasprowicz Katarzyna , Rita-Tkachenko Patrycja , Renke Marcin , Ratkowski Wojciech
Published: May 2019

Background and Objectives: Physical exercise increases the blood perfusion of muscles, but decreases the renal blood flow. There are several markers of renal hypoperfusion which are used in the differential diagnosis of acute kidney failure. Albuminuria is observed after almost any exercise. The aim of this study was to assess changes in renal hypoperfusion and albuminuria after a 100-km race. Materials and Methods: A total of 27 males who finished a 100-km run were studied. The mean age of the runners was 38.04 ± 5.64 years. The exclusion criteria were a history of kidney disease, glomerular filtration rate (GFR) <60 ml/min, and proteinuria. Blood and urine were collected before and after the race. The urinary albumin/creatinine ratio (ACR), fractional excretion of urea (FeUrea) and sodium (FeNa), plasma urea/creatinine ratio (sUrea/Cr), urine/plasma creatinine ratio (u/pCr), urinary sodium to potassium ratio (uNa/K), and urinary potassium to urinary potassium plus sodium ratio (uK/(K+Na)) were calculated. Results: After the race, significant changes in albuminuria and markers of renal hypoperfusion (FeNa, FeUrea, sUrea/Cr, u/sCr, urinary Na, uNa/K, uK/(K+Na)) were found. Fifteen runners (55.56%) had severe renal hypoperfusion (FeUrea <35, uNa/K <1, and uK/(Na+K) >0.5) after the race. The mean ACR increased from 6.28 ± 3.84 mg/g to 48.43 ± 51.64 mg/g (p < 0.001). The ACR was higher in the group with severe renal hypoperfusion (59.42 ± 59.86 vs. 34.68 ± 37.04 mg/g), but without statistical significance. Conclusions: More than 50% of the runners had severe renal hypoperfusion after extreme exercise. Changes in renal hemodynamics are probably an important, but not the only, factor of post-exercise proteinuria.
Increased Glomerular Filtration Rate in Early Stage of Balkan Endemic Nephropathy
Authors: Djukanović Ljubica , Ležaić Višnja , Bukvić Danica , Mirković Dušan , Marić Ivko
Published: May 2019

Background: A previous study indicated that Balkan endemic nephropathy (BEN) patients in the early stage of the disease had significantly higher creatinine clearance (Ccr) than healthy persons. The aim of the study was to assess whether tubular creatinine secretion affects Ccr in early stages of BEN and to check the applicability of serum creatinine-based glomerular filtration rate (GFR) equations in these patients. Methods: The study involved 21 BEN patients with estimated GFR (eGFR) above 60 mL/min/1.73 m2, excluding any conditions that could affect GFR or tubular creatinine secretion, and 15 healthy controls. In all participants Ccr with and without cimetidine and iohexol clearance (mGFR) were measured and eGFR calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease Study (MDRD) equations. Glomerular hyperfiltration cutoff (GFR-HF) was calculated. Results: There was no significant difference between the groups in Ccr before and after cimetidine or for eGFR, but mGFR was significantly higher in BEN patients than in controls (122.02 ± 28.03 mL/min/1.73 m2 vs. 101.15 ± 27.32 mL/min/1.73 m2; p = 0.032). Cimetidine administration reduced Ccr by 10% in both groups. The ratio of Ccr to mGFR was significantly above one in seven BEN patients and five controls and their mGFR values were similar. Seven other patients and eight controls had this ratio equal to one, while values below one were recorded for seven more patients and two controls. mGFR of all these 14 patients was significantly higher than that of healthy controls (129.88 ± 27.52 mL/min/1.73 m2 vs. 107.43 ± 19.51 mL/min/1.73 m2; p = 0.009). Mean GFR-HF was significantly higher than mGFR in controls, but these two values were similar in BEN patients. eGFR underestimated mGFR in both BEN patients and controls. Conclusion: The ratio of Ccr to mGFR and mGFR to GFR-HF indicated that elevated mGFR in early stages of BEN could be explained by increased glomerular filtration, but tubular creatinine secretion augmented Ccr in a smaller proportion of patients, who did not differ from healthy subjects.
Optimal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Cut-Offs: A Cross-Sectional Study in the Czech Population
Authors: Horáková Dagmar , Štěpánek Ladislav , Janout Vladimír , Janoutová Jana , Pastucha Dalibor , Kollárová Helena , Petráková Alena , Štěpánek Lubomír , Husár Roman , Martiník Karel
Published: May 2019

Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we aimed to define the cut-offs for the Czech population. Methods: After undergoing anthropometric and biochemical studies, the sample of 3539 individuals was divided into either nondiabetics, including both subjects with normal glucose tolerance (NGT, n = 1947) and prediabetics (n = 1459), or diabetics (n = 133). The optimal HOMA-IR cut-offs between subgroups were determined to maximize the sum of the sensitivity and specificity for diagnosing type 2 diabetes mellitus (T2DM) or prediabetes. The predictive accuracy was illustrated using receiver operating characteristic (ROC) curves. Logistic regression was performed to assess the association between a target variable (presence/absence of T2DM) depending on the HOMA-IR score as well as on the age and sex. Results: The HOMA-IR cut-off between nondiabetics and diabetics for both sexes together was 3.63, with a sensitivity of 0.56 and a specificity of 0.86. The area under the ROC curve was 0.73 for T2DM diagnosing in both sexes. The HOMA-IR cut-off between the NGT subjects and prediabetics was 1.82, with a sensitivity of 0.60 and a specificity of 0.66. Logistic regression showed that increased HOMA-IR is a risk factor for the presence of T2DM (odds ratio (OR) 1.2, 95% confidence interval (CI) 1.14–1.28, p < 0.0001). The predictive ability of HOMA-IR in diagnosing T2DM is statistically significantly lower in females (OR 0.66, 95% CI 0.44–0.98). The results are valid for middle-aged European adults. Conclusions: The results suggest the existence of HOMA-IR cut-offs signaling established IR. Introduction of the instrument into common clinical practice, together with the known cut-offs, may contribute to preventing T2DM.
Pirfenidone Improves Familial Idiopathic Pulmonary Fibrosis without Affecting Serum Periostin Levels
Authors: Koga Yasuhiko , Hachisu Yoshimasa , Tsurumaki Hiroaki , Yatomi Masakiyo , Kaira Kyoichi , Ohta Shoichiro , Ono Junya , Izuhara Kenji , Dobashi Kunio , Hisada Takeshi
Published: May 2019

Background: Antifibrotic agents have been approved for the treatment of idiopathic pulmonary fibrosis (IPF). However, the efficacy of these drugs in the treatment of familial IPF (FIPF) has not been previously reported. Case presentation: We report the case of a 77-year-old man with FIPF, successfully treated with pirfenidone. His uncle died due to IPF, and his niece was diagnosed with the disease. He had worsening dyspnea two months prior to admission to our hospital. Upon admission, he had desaturation when exercising and broad interstitial pneumonia. Administration of pirfenidone improved his dyspnea, desaturation, and the reticular shadow on his chest radiograph. Increased fibrotic marker levels KL-6 and SP-D were also normalized in six months; treatment had no effect on his serum periostin level. Pirfenidone has been effective for over two years. Conclusion: Antifibrotic agents such as pirfenidone may be useful for the management of FIPF, as well as cases of sporadic IPF.
Challenges to Be Tackled in the Computational Modeling and Numerical Simulation of FSW Processes
Authors: Agelet De Saracibar Carlos
Published: May 2019

The computational modeling and numerical simulation of Friction Stir Welding (FSW) processes is an extremely challenging task due to the highly nonlinear and coupled nature of the physical problem and the complex computational issues that need to be properly tackled in the numerical model [...]
Additive Manufacturing of Complex Components through 3D Plasma Metal Deposition—A Simulative Approach
Authors: Alaluss Khaled , Mayr Peter
Published: May 2019

This study examines simulative experimental investigations on the additive manufacturing of complex component geometries using 3D plasma metal deposition (3DPMD). Here, complex contour surfaces for a cross-rolling tool were produced from weld metals in multilayer technology through 3DPMD. As a consequence of the special features of 3DPMD with large-weld metal volumes, greatly differing properties between base material/deposited material and asymmetrical heat input, the resulting shrinkage, deformation and residual stresses are particularly critical. These lead to dimensional and form deviations as well as the formation of cracks, which has a negative influence on the quality of the plasma deposition-welded component structures. By means of the thermo-elastic-plastic simulation model, the temperature field distribution, deformation, and residual stresses occurring during additive 3DPMD of tool contours were predicted and analyzed. The temperature field distribution and its gradients were determined using the ellipsoid heat-source model for the 3DPMD process. On this basis, a coupled thermo-elastic-plastic structural–mechanical analysis was performed. Accordingly, the results achieved were used for the production of almost-net-shaped tool contour surfaces with predefined layer properties. The acquired simulation results of the temperature fields, deformation, and residual stress condition show good alignment with the experimental results.
Austenite Reversion Tempering-Annealing of 4 wt.% Manganese Steels for Automotive Forging Application
Authors: Gramlich Alexander , Emmrich Robin , Bleck Wolfgang
Published: May 2019

New medium Mn steels for forged components, in combination with a new heat treatment, are presented. This new annealing process implies air-cooling after forging and austenite reversion tempering (AC + ART). This leads to energy saving compared to other heat treatments, like quenching and tempering (Q + T) or quenching and partitioning (Q + P). Furthermore, the temperature control of AC + ART is easy, which increases the applicability to forged products with large diameters. Laboratory melts distinguished by Ti, B, Mo contents have been casted and consecutively forged into semi-finished products. Mechanical properties and microstructure have been characterized for the AC and the AC + ART states. The as forged-state shows YS from 900 MPa to 1000 MPa, UTS from 1350 MPa to 1500 MPa and impact toughness from 15 J to 25 J. Through the formation of nanostructured retained metastable austenite an increase in impact toughness was achieved with values from 80 J to 100 J dependent on the chemical composition.
The Effect of Initial Annealing Microstructures on the Forming Characteristics of Ti–4Al–2V Titanium Alloy
Authors: Yan Bin , Li Hongbo , Zhang Jie , Kong Ning
Published: May 2019

In this study, the effect of initial annealing microstructure of Ti–4Al–2V (TA17) alloy on forming characteristic was studied, so as to provide a basis for quality control of plastic forming of titanium alloy parts. The titanium alloy always undergoes annealing treatment before forming, due to different microstructures present different mechanical properties. The TA17 with different microstructures are obtained by means of various annealing treatment temperatures. The tensile behavior of TA17 is investigated at room temperature and 900 °C under constant strain rate of 0.01 s−1. The experimental results show that the mechanical properties of TA17 are sensitive to the initial microstructure before deformation. The microstructure of TA17 at 850 °C (2 h) is the equiaxed primary α-phase after the annealing process. It exhibits good plasticity at room temperature. This phenomenon is also confirmed from fracture morphology from the scanning electron microscope (SEM) analysis. At 900 °C, which is a high tensile temperature, the alloy with equiaxed primary α-phase performs outstanding plasticity compared with other microstructures. This work establishes a good understanding on the relationship between the mechanical properties and microstructures of TA17 at a wide temperature range.
Effects of Long-Term Storage at −80 °C on the Human Plasma Metabolome
Authors: Wagner-Golbs Antje , Neuber Sebastian , Kamlage Beate , Christiansen Nicole , Bethan Bianca , Rennefahrt Ulrike , Schatz Philipp , Lind Lars
Published: May 2019

High-quality biological samples are required for the favorable outcome of research studies, and valid data sets are crucial for successful biomarker identification. Prolonged storage of biospecimens may have an artificial effect on compound levels. In order to investigate the potential effects of long-term storage on the metabolome, human ethylenediaminetetraacetic acid (EDTA) plasma samples stored for up to 16 years were analyzed by gas and liquid chromatography-tandem mass spectrometry-based metabolomics. Only 2% of 231 tested plasma metabolites were altered in the first seven years of storage. However, upon longer storage periods of up to 16 years and more time differences of few years significantly affected up to 26% of the investigated metabolites when analyzed within subject age groups. Ontology classes that were most affected included complex lipids, fatty acids, energy metabolism molecules, and amino acids. In conclusion, the human plasma metabolome is adequately stable to long-term storage at −80 °C for up to seven years but significant changes occur upon longer storage. However, other biospecimens may display different sensitivities to long-term storage. Therefore, in retrospective studies on EDTA plasma samples, analysis is best performed within the first seven years of storage.
Urate and Nonanoate Mark the Relationship between Sugar-Sweetened Beverage Intake and Blood Pressure in Adolescent Girls: A Metabolomics Analysis in the ELEMENT Cohort
Authors: Perng Wei , Tang Lu , Song Peter X. K. , Goran Michael , Tellez Rojo Martha Maria , Cantoral Alejandra , Peterson Karen E.
Published: May 2019

We sought to identify metabolites that mark the relationship of sugar-sweetened beverage (SSB) intake with adiposity and metabolic risk among boys (n = 114) and girls (n = 128) aged 8–14 years. We conducted the analysis in three steps: (1) linear regression to examine associations of SSB intake (quartiles) with adiposity, glycemia, lipids, and blood pressure (BP); (2) least absolute shrinkage and selection operator (LASSO) regression to identify SSB-associated metabolites from an untargeted dataset of 938 metabolites; and (3) linear regression to determine whether SSB-related metabolites are also associated with adiposity and metabolic risk. In girls, SSB intake was associated with marginally higher BP (Q2 vs, Q1: 1.11 [−3.90, 6.13], Q3 vs. Q1: 1.16 [−3.81, 6.13], Q4 vs. Q1: 4.65 [−0.22, 9.53] mmHg systolic blood pressure (SBP); P-trend = 0.07). In boys, SSB intake corresponded with higher C-peptide insulin resistance (Q2 vs. Q1: 0.06 [−0.06, 0.19], Q3 vs. Q1: 0.01 [−0.12, 0.14], Q4 vs. Q1: 0.17 [0.04, 0.30] ng/mL; P-trend = 0.03) and leptin (P-trend = 0.02). LASSO identified 6 annotated metabolites in girls (5-methyl-tetrohydrofolate, phenylephrine, urate, nonanoate, deoxyuridine, sn-glycero-3-phosphocholine) and 3 annotated metabolites in boys (2-piperidinone, octanoylcarnitine, catechol) associated with SSB intake. Among girls, urate and nonanoate marked the relationship of SSB intake with BP. None of the SSB-associated metabolites were related to health outcomes in boys.
Study of the Adhesion Mechanism of Acidithiobacillus ferrooxidans to Pyrite in Fresh and Saline Water
Authors: San Martín Francisca , Aguilar Claudio
Published: May 2019

In the present work, the streaming potential of A. ferrooxidans and pyrite was measured in two environments: fresh and saline water (water with 35 g/L of NaCl) at different pH values. Also, attachment kinetics of A. ferrooxidans to pyrite was studied in fresh and saline water at pH 4. The results show that A. ferrooxidans and pyrite had lower streaming potentials (comparing absolute values) in saline water than in fresh water, indicating the compression in the electrical double layer caused by Cl− and Na+ ions. It was also determined that the bacteria had a higher level of attachment to pyrite in fresh water than in saline water. The high ionic strength of saline water reduced the attractive force between A. ferrooxidans and pyrite, which in turn reduced bacterial attachment. Electrostatic interactions were determined to be mainly repulsive, since the bacteria and mineral had the same charge at pH 4. Despite this, the bacteria adhered to pyrite, indicating that hydrophobic attraction forces and Lifshitz–van der Waals interactions were stronger than electrostatic interactions, which caused the adhesion of A. ferrooxidans to pyrite.
Structure, Shift in Redox Potential and Li-Ion Diffusion Behavior in Tavorite LiFe1−xVxPO4F Solid-Solution Cathodes
Authors: Yan Jia-Li , Shao Gang-Qin , Fan Shu-Hao , Zhu Can , Zhang Yong , Wang Jun , Liu Qi
Published: May 2019

Solid-solution Li-ion cathode materials transform through a single-phase reaction thus leading to a long-term structural stability and improved cyclability. In this work, a two- to single-phase Li+-extraction/insertion mechanism is studied through tuning the stoichiometry of transition-metal Fe/V cations to trigger a transition in the chemical reactivity path. Tavorite triclinic-structured LiFe1−xVxPO4F (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1) solid-solution powders were prepared by a facile one-step solid-state method from hydrothermal-synthesized and commercial raw materials. The broad shape of cyclic voltammetry (CV) peaks, sloping charge/discharge profiles and sloping open-circuit voltage (OCV) profiles were observed in LiFe1−xVxPO4F solid-solution cathodes while 0 < x < 1. These confirm strongly a single-phase behavior which is different from the two-phase behavior in the end-members (x = 0 or 1). The electronegativity of M (M = Fe1−xVx) for the redox potential of Fe2+/3+ couple or the M–O4F2 bond length for the V3+/4+ couple plays respectively a dominant role in LiFe1−xVxPO4F solid-solution cathodes.
Clitoria ternatea Flower Petal Extract Inhibits Adipogenesis and Lipid Accumulation in 3T3-L1 Preadipocytes by Downregulating Adipogenic Gene Expression
Authors: Chayaratanasin Poramin , Caobi Allen , Suparpprom Chaturong , Saenset Sudarat , Pasukamonset Porntip , Suanpairintr Nipattra , Barbieri Manuel Alejandro , Adisakwattana Sirichai
Published: May 2019

Clitoria ternatea (commonly known as blue pea) flower petal extract (CTE) is used as a natural colorant in a variety of foods and beverages. The objective of study was to determine the inhibitory effect of CTE on adipogenesis in 3T3-L1 preadipocytes. The phytochemical profiles of CTE were analyzed by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Anti-adipogenesis effect of CTE was measured by using Oil Red O staining, intracellular triglyceride assay, quantitative real-time PCR and western blot analysis in 3T3-L1 adipocytes. Cell cycle studies were performed by flow cytometry. Lipolysis experiments were performed using a colorimetric assay kit. In early stages, CTE demonstrated anti-adipogenic effects through inhibition of proliferation and cell cycle retardation by suppressing expression of phospho-Akt and phospho-ERK1/2 signaling pathway. The results also showed that CTE inhibited the late stage of differentiation through diminishing expression of adipogenic transcription factors including PPARγ and C/EBPα. The inhibitory action was subsequently attenuated in downregulation of fatty acid synthase and acetyl-CoA carboxylase, causing the reduction of TG accumulation. In addition, CTE also enhanced catecholamine-induced lipolysis in adipocytes. These results suggest that CTE effectively attenuates adipogenesis by controlling cell cycle progression and downregulating adipogenic gene expression.
Imaging Flow Cytometric Analysis of Stilbene-Dependent Apoptosis in Drug Resistant Human Leukemic Cell Lines
Authors: Czop Marcin , Bogucka-Kocka Anna , Kubrak Tomasz , Knap-Czop Karolina , Makuch-Kocka Anna , Galkowski Dariusz , Wawer Joanna , Kocki Tomasz , Kocki Janusz
Published: May 2019

Background: The natural compounds have been researched extensively as an alternative to the conventional chemotherapy and radiation. Stilbene derivatives appear as a group of therapeutics which deserves special attention. The present study was designed to analyze the effects of stilbene derivatives on drug resistant human leukemic cells. The aim of this work was to evaluate the apoptotic effect of stilbene derivatives in various concentrations on leukemic cells (LC) with and without resistant phenotype. Methods: Human acute promyelocytic leukemia (APL) cell lines (HL60, HL60/MX1, HL60/MX2) and acute lymphoblastic leukemia (ALL) cell lines (CEM/C1, CCRF-CEM) were studied. T-resveratrol, piceatannol, rhaponticin, deoxyrhaponticin, pterostilbene were used to stimulate apoptosis. Mitoxantrone (MIT) was applied to induce drug resistance. Results: t-Resveratrol (RES), deoxyrhaponticin (D-RHAP), rhaponticin (RHAP), pterostilbene (PTER), and piceatannol (PIC) influenced viability and induced apoptosis in all investigated cell lines. Conclusions: Our results confirmed that RES, PIC, RHAP, D-RHAP, and PTER are essential therapeutic compounds with anticancer activity exhibited by induction of apoptosis in leukemic cells with and without resistant phenotype. Stilbene-induced apoptosis in HL60/MX1, HL60/MX2, CEM/C1, and CCRF-CEM leukemia cell lines have been presented in very few studies so far and our research is an important contribution to the investigation of these substances.
Pharmacodynamics of Five Anthraquinones (Aloe-emodin, Emodin, Rhein, Chysophanol, and Physcion) and Reciprocal Pharmacokinetic Interaction in Rats with Cerebral Ischemia
Authors: Li Rong-Rong , Liu Xue-Fang , Feng Su-Xiang , Shu Sheng-Nan , Wang Pei-Yang , Zhang Na , Li Jian-Sheng , Qu Ling-Bo
Published: May 2019

(1) Background: Rhubarb anthraquinones—a class of components with neuroprotective function—can be used to alleviate cerebral ischemia reperfusion injury. (2) Methods: The three pharmacodynamic indicators are neurological function score, brain water content, and cerebral infarction area; UPLC-MS/MS was used in pharmacokinetic studies to detect plasma concentrations at different time points, and DAS software was used to calculate pharmacokinetic parameters in a noncompartmental model. (3) Results: The results showed that the pharmacodynamics and pharmacokinetics of one of the five anthraquinone aglycones could be modified by the other four anthraquinones, and the degree of interaction between different anthraquinones was different. The chrysophanol group showed the greatest reduction in pharmacodynamic indicators comparing with other four groups where the rats were administered one of the five anthraquinones, and there was no significant difference between the nimodipine group. While the Aloe-emodin + Physcion group showed the most obvious anti-ischemic effect among the groups where the subjects were administered two of the five anthraquinones simultaneously. Emodin, rhein, chrysophanol, and physcion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lower their plasma exposure levels. (4) Conclusions: This experiment provides a certain preclinical basis for the study of anthraquinone aglycones against cerebral ischemia and a theoretical basis for the study of the mechanism of interaction between anthraquinones.
Proteomics Research on the Protective Effect of Mangiferin on H9C2 Cell Injury Induced by H2O2
Authors: Guan Wei , Liu Yan , Liu Yuan , Wang Qi , Ye Hong-Liang , Cheng Yan-Gang , Kuang Hai-Xue , Jiang Xi-Cheng , Yang Bing-You
Published: May 2019

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide. Mangiferin is a natural glucosylxanthone with antioxidant and anti-inflammatory properties, which has been confirmed to protect cardiac cells from myocardial infarction and myocardial ischemia reperfusion injury (MIRI); however, the underlying mechanism is still unclear. As oxidative stress is a major pathogenesis of MIRI, an H9C2 cell injury induced by hydrogen peroxide (H2O2) was established to simulate MIRI in vitro. Herein, the protective effect of mangiferin against MIRI was evaluated and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics was applied to explore the underlying molecular mechanism. In this research, mangiferin markedly ameliorated the oxidative imbalance by increasing the antioxidative capacity of the H9C2 cell. Moreover, proteomics analysis revealed that mangiferin pretreatment brought twenty differently-expressed proteins back to normal, most of which were related to glucose and fatty acid metabolism. Glycolysis, citrate cycle, and fatty acid degradation pathways were highlighted by Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis. Western blot validation of six cardiac metabolism-related proteins were consistent with the proteomics analysis. Taken together, mangiferin protected the cardiomyocytes from MIRI by enhancing the antioxidant capacity and increasing the activities of glycolysis, citrate cycle, and fatty acid degradation pathways.
Applying Aluminum–Vertically-Aligned Carbon Nanotube Forests Composites for Heat Dissipation
Authors: Li Yan-Rui , Su Chih-Chung , Chang Shuo-Hung
Published: May 2019

Vertically-aligned carbon nanotube forests (VACNTs) with excellent axial heat dissipation properties were formed on aluminum foil to dissipate heat. In addition, the heat dissipation efficiency of aluminum–VACNTs composites in this work was compared with that of commercially available mainstream thermal sheets under the same natural cooling conditions. Chemical vapor deposition (CVD) was employed as a synthesis method using a three-segment high-temperature furnace. Subsequently, the temperature changes in a heating body with the aluminum–VACNTs composites was measured over time subject to natural cooling. In addition, the performance was compared with copper and pyrolytic graphite sheets. The experimental results revealed that the heat dissipation efficiency of the flexible aluminum–VACNTs composites was higher than that of clean aluminum foil, a copper sheet, and a pyrolytic graphite sheet by up to 56%, 40%, and 20%, respectively. Moreover, this work also verified the height of the carbon nanotube (CNT) did not influence the heat dissipation efficiency, indicating that the time cost of synthesis could be reduced.