bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Cloning and Characterization of a meta/para-O-Methyltransferase from Lycoris aurea
Authors: Sun Bin , Wang Peng , Wang Ren , Li Yikui , Xu Sheng
Published: June 2018

O-methyltransferases (OMTs) have been demonstrated to play key roles in the biosynthesis of plant secondary metabolites, such as alkaloids, isoprenoids, and phenolic compounds. Here, we isolated and characterized an OMT gene from Lycoris aurea (namely LaOMT1), based on our previous transcriptome sequencing data. Sequence alignment and phylogenetic analysis showed that LaOMT1 belongs to the class I OMT, and shares high identity to other known plant OMTs. Also, LaOMT1 is highly identical in its amino acid sequence to NpN4OMT, a norbelladine 4′-OMT from Narcissus sp. aff. pseudonarcissus involved in the biosynthesis of Amaryllidaceae alkaloids. Biochemical analysis indicated that the recombinant LaOMT1 displayed both para and metaO-methylation activities with caffeic acid and 3,4-dihydroxybenzaldehyde, and showed a strong preference for the meta position. Besides, LaOMT1 also catalyzes the O-methylation of norbelladine to form 4′-O-methylnorbelladine, which has been demonstrated to be a universal precursor of all the primary Amaryllidaceae alkaloid skeletons. The results from quantitative real-time PCR assay indicated that LaOMT1 was ubiquitously expressed in different tissues of L. aurea, and its highest expression level was observed in the ovary. Meanwhile, the largest concentration of lycorine and galanthamine were found in the ovary, whereas the highest level of narciclasine was observed in the bulb. In addition, sodium chloride (NaCl), cold, polyethylene glycol (PEG), sodium nitroprusside (SNP), and methyl jasmonate (MeJA) treatments could significantly increase LaOMT1 transcripts, while abscisic acid (ABA) treatment dramatically decreased the expression level of LaOMT1. Subcellular localization showed that LaOMT1 is mainly localized in cytoplasm and endosome. Our results in this study indicate that LaOMT1 may play a multifunctional role, and lay the foundation for Amaryllidaceae alkaloid biosynthesis in L. aurea.
Nitric Oxide Is Required for Melatonin-Enhanced Tolerance against Salinity Stress in Rapeseed (Brassica napus L.) Seedlings
Authors: Zhao Gan , Zhao Yingying , Yu Xiuli , Kiprotich Felix , Han Han , Guan Rongzhan , Wang Ren , Shen Wenbiao
Published: June 2018

Although melatonin (N-acetyl-5-methoxytryptamine) could alleviate salinity stress in plants, the downstream signaling pathway is still not fully characterized. Here, we report that endogenous melatonin and thereafter nitric oxide (NO) accumulation was successively increased in NaCl-stressed rapeseed (Brassica napus L.) seedling roots. Application of melatonin and NO-releasing compound not only counteracted NaCl-induced seedling growth inhibition, but also reestablished redox and ion homeostasis, the latter of which are confirmed by the alleviation of reactive oxygen species overproduction, the decreases in thiobarbituric acid reactive substances production, and Na+/K+ ratio. Consistently, the related antioxidant defense genes, sodium hydrogen exchanger (NHX1), and salt overly sensitive 2 (SOS2) transcripts are modulated. The involvement S-nitrosylation, a redox-based posttranslational modification triggered by NO, is suggested. Further results show that in response to NaCl stress, the increased NO levels are strengthened by the addition of melatonin in seedling roots. Above responses are abolished by the removal of NO by NO scavenger. We further discover that the removal of NO does not alter endogenous melatonin content in roots supplemented with NaCl alone or together with melatonin, thus excluding the possibility of NO-triggered melatonin production. Genetic evidence reveals that, compared with wild-type Arabidopsis, the hypersensitivity to NaCl in nia1/2 and noa1 mutants (exhibiting null nitrate reductase activity and indirectly reduced endogenous NO level, respectively) cannot be rescued by melatonin supplementation. The reestablishment of redox homeostasis and induction of SOS signaling are not observed. In summary, above pharmacological, molecular, and genetic data conclude that NO operates downstream of melatonin promoting salinity tolerance.
Cynoglossus semilaevis Rspo3 Regulates Embryo Development by Inhibiting the Wnt/β-Catenin Signaling Pathway
Authors: Niu Jingjing , Guan Jian , Li Rui , Li Xuemei , Zhai Jieming , Qi Jie , He Yan
Published: June 2018

Cynoglossus semilaevis is an important economic fish species and has long been cultivated in China. Since the completion of its genome and transcriptome sequencing, genes relating to C. semilaevis development have been extensively studied. R-spondin 3 (Rspo3) is a member of the R-spondin family. It plays an important role in biological processes such as vascular development and oncogenesis. In this study, we cloned and characterized the expression patterns and functions of C. semilaevisRspo3. Initial structural and phylogenetic analyses revealed a unique FU3 domain that exists only in ray-finned fish RSPO3. Subsequent embryonic expression profile analysis showed elevating expression of Rspo3 from gastrulation to the formation of the eye lens, while, in tail bud embryos, Rspo3 expression was significantly high in the diencephalon and mesencephalon. The overexpression of C. semilaevis Rspo3 in Danio rerio embryos resulted in a shortened rostral–caudal axis, edema of the pericardial cavity, stubby yolk extension, and ecchymosis. Vascular anomalies were also observed, which is consistent with Rspo3 role in vascular development. Drug treatment and a dual-luciferase reporter assay confirmed the inhibitory role of C. semilaevis Rspo3 in D. rerio Wnt/β-catenin signaling pathway. We further concluded that the FU2, FU3, and TSP1 domains regulate the maternal Wnt/β-catenin signaling pathway, while the FU1 domain regulates the zygotic Wnt/β-catenin signaling pathway. This study enriches Rspo3 research in non-model animals and serves as the basis for further research into the interactions between Rspo and the Wnt/β-catenin signaling pathway.
An Unusual and Fatal Cause of Miliary Nodules on Chest Radiography
Authors: Cheema Anmol , Chaughtai Saira , Mazahir Usman , Roy Manimala , Hossain Mohammad
Published: June 2018

Foreign body granulomatosis has many etiologies, including the injection of oral medications intravenously. The insoluble filler materials that are used in the medications can lodge in pulmonary arterioles and capillaries, which can trigger foreign body giant cell reaction, chronic inflammation, thrombosis, and fibrosis, resulting in pulmonary hypertension, progressive shortness of breath, and, potentially, fatal conditions. On imaging, this may present with multiple miliary mottling’s/nodules. The use of a bronchoscopy with biopsy can be an excellent way to establish a diagnosis in appropriate clinical settings. Here, we present a case of a 37-year-old old male found to have multiple miliary densities on imaging due to intravenous use of oral medication.
Technology-Enhanced Classroom Activity Breaks Impacting Children’s Physical Activity and Fitness
Authors: Buchele Harris Heidi , Chen Weiyun
Published: June 2018

Background: This study examined the effects of a 4-week technology-enhanced physical activity (PA) interventions on students’ real-time daily PA and aerobic fitness levels. Methods: 116 fifth-graders were assigned to one intervention group (n = 31) participating in daily physical activity engaging the brain with Fitbit Challenge (PAEB-C), another intervention group (n = 29) wearing Fitbits only (Fitbit-O) daily, five days per week, or the comparison group (n = 56). Four-week real-time PA data were collected from the intervention students via Fitbase. Three groups were pre- and post-tested aerobic fitness. Results: The PAEB-C students showed significantly higher steps and minutes of being very active and fairly active (F = 7.999, p = 0.014, ŋ = 0.121; F = 5.667, p = 0.021, ŋ = 0.089; F = 10.572, p = 0.002, ŋ = 0.154) and lower minutes of being sedentary daily (F = 4.639, p = 0.035, ŋ = 0.074) than the Fitbit-O group. Both Fitbit groups exhibited significantly greater increases in aerobic fitness scores than the comparison group over time (F = 21.946, p = 0.001, ŋ = 0.303). Boys were more physically active and fit than girls. Conclusions: Technology-enhanced PA intervention was effective for improving real-time PA and aerobic fitness.
Paradigm Shift or Paradigm Paralysis? National Mental Health and Capacity Law and Implementing the CRPD in Scotland
Authors: Stavert Jill
Published: June 2018

The United Nations Convention on the Rights of Persons with Disabilities (CRPD) highlights the need to actively remove obstacles to, and promote, the full and equal enjoyment of human rights by persons with disabilities. This is challenging us to revisit existing conceptions about what is genuine equal and non-discriminatory enjoyment of human rights by persons with cognitive, intellectual and psychosocial disabilities and to accept that a real and fundamental culture change is required in order to achieve this. Whilst many states are seeking to address CRPD requirements in law and policy, including those identified in its Article 12, it is arguable that these do not go far enough in order to secure this culture change. This article considers three issues that need to be resolved as part of the process of achieving this paradigm shift, namely capacity assessments as thresholds for involuntary interventions, authorising involuntary interventions and support for the exercise of legal capacity, both generally and in the particular context of Scotland’s mental health and capacity laws. In doing so, it argues that it is debatable whether the CRPD paradigm shift can be realistically achieved by simply adapted or supplementing current legal and policy models.
Fabrication of Superhydrophobic Mg/Al Layered Double Hydroxide (LDH) Coatings on Medium Density Fiberboards (MDFs) with Flame Retardancy
Authors: Wang Zhe , Shen Xiaoping , Qian Temeng , Xu Kang , Sun Qingfeng , Jin Chunde
Published: June 2018

The hydrophilicity and flammability of fiberboards have limited their real-life applications. In this study, a facile strategy for preparing the multifunctional coatings with superhydrophobicity and flame retardancy on medium density fiberboards (MDFs) has been investigated. The superhydrophobic and flame-retardant coating on the MDF surface was obtained by depositing polydimethylsiloxane (PDMS) and 1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane (FDTS)-modified Mg/Al layered double hydroxide (LDH) particles step by step. The as-prepared coating exhibited superhydrophobic properties with a water contact angle (WCA) of ~155° and good self-cleaning properties. Furthermore, the limiting oxygen index (LOI) value of the superhydrophobic MDFs increased by 60.4% as compared to that of the pristine MDFs, showing improved flame retardancy. The peak heat release rate (PHRR) and total heat release (THR) of MDFs decreased after coating with PDMS@FDTS-Mg/Al LDH, suggesting that the superhydrophobic coating decreased the fire growth speed and risk of fire hazard of MDFs. This coating with multiple functions opens a new avenue for the protection and functionalization of MDFs.
Structure and Properties of Zr-Based Bulk Metallic Glasses in As-Cast State and After Laser Welding
Authors: Pilarczyk Wirginia
Published: June 2018

Laser-beam fusion welding processes enable the increase of the size of metallic glass parts, and therefore facilitate the application of this new material in different products. To get exceptional properties of the material after the welding process, characteristics of the weld structure in the heat affected zone and in the fusion zone should be predicted. The main goal of this work is to study the structure and specific characteristics of the Zr55Cu30Ni5Al10 alloy after the casting process and after the laser welding process. Electron microscopy observation confirmed that the amorphous phase was present in the fusion zone and amorphous–crystalline phase was present in the heat-affected zone. Higher nanohardness and reduced Young’s modulus values were demonstrated for laser welds using higher impulse energy (2.78 J) and impulse peak power (1000 W).
Elucidation of the Relationship between CD Cotton Effects and the Absolute Configuration of Sixteen Stereoisomers of Spiroheterocyclic-Lactams
Authors: Yamada Takeshi , Kajimoto Tetsuya , Kikuchi Takashi , Tanaka Reiko
Published: June 2018

As part of research to search for antitumor agents in fungi originating from marine organisms, cephalimysins E–L were isolated from a culture broth of Aspergillus fumigatus that was separated from the marine fish Mugil cephalus. One- and two-dimensional nuclear magnetic resonance spectra revealed their planar structures, which are diastereomers of each other. Their absolute stereostructures were established by epimerization at C-8 with acidic methanol, nuclear Overhauser effect spectroscopy (NOESY), and circular dichroism (CD) spectroscopy. These demonstrated the detailed relationships between absolute configuration and CD Cotton effects. Additionally, in the growth inhibition assay against P388, HL-60, L1210, and KB cell lines, some of the fungal metabolites or reaction products exhibited moderate activities.
Stents in interventional cardiology
Authors: Grinius Virgilijus , Navickas Ramūnas , Unikas Ramūnas
Published: June 2018

Since the first percutaneous transluminal coronary angioplasty performed by A. Gruentzig in 1977, percutaneous coronary interventions have become the most important treatment modality for coronary heart disease. Coronary angioplasty carried a significant risk of coronary flow-limiting dissections and restenosis during the first six months following the procedure. Two main studies comparing percutaneous transluminal coronary angioplasty and coronary stenting (STRESS and BENESTENT) performed in 1994 showed a significant reduction in restenosis rate using stents. Thus, until now stents are the most widely used devices for coronary intervention despite two problems: subacute stent thrombosis (1–2%) and still high restenosis rate (5–40%). Subacute stent thrombosis occurs within the first month after stent placement and can be prevented using the double antiplatelet regimen with aspirin and clopidogrel. Some risk of subacute thrombosis remains beyond the first month when drug-eluting stents are used. This requires prolonged antiplatelet therapy. Drugeluting stents are the most significant innovation in interventional cardiology. They can reduce the incidence of restenosis in native stable coronary arteries to 3–5%. However, the long-term studies comparing bare-metal stents and drug-eluting stents did not show any significant differences in the rate of major adverse cardiac events (death, myocardial infarction), especially in patients with diabetes after the treatment of bifurcational lesions. According to proposed recommendations, drug-eluting stents should be used in small vessels, restenotic lesions, and in saphenous vein grafts. Despite some disadvantages, the results of coronary stenting using drugeluting stents continue to improve.
Effects of the prolonged thoracic epidural analgesia on ventilation function and complication rate after the lung cancer surgery
Authors: Kopeika Uldis , Taivans Immanuels , Ūdre Sanita , Jakušenko Nataļja , Strazda Gunta , Mihelsons Māris
Published: June 2018

Thoracic epidural analgesia has been considered to have a good anesthetic efficacy and to decrease the postoperative complication rate, while its effect upon the ventilation function is still the topic of many clinical studies. The aim of this study was to evaluate the course of early postoperative period using thoracic epidural analgesia. Material and methods. A total of 453 patients undergoing the operation due to the non–small cell carcinoma were selected and examined. Their postoperative complications and mortality rate were evaluated. In 79 patients, arterial oxygen saturation (SaO2), forced vital capacity, forced expiratory volume in the first second, and the efficacy of analgesia were analyzed within the first 7 days after the operation. These patients were divided into subgroups according to the type of the operation – lobectomy or pneumonectomy – and the type of analgesia – thoracic epidural analgesia or opiates administered intramuscularly (control group). Results. A better statistically significant efficacy of analgesia was observed in thoracic epidural analgesia group than in the control group (visual analog pain scale score 2.5 versus 5.3, P<0.01). There was also a statistically significant lower incidence of postoperative complications (20.5% versus 38.8%, respectively). Thoracic epidural analgesia is a factor decreasing the relative risk of complications (RR=0.53, 95% CI 0.28–0.99, P=0.0233). In the lobectomy group, 24 hours after the surgery, forced vital capacity was 61±12% in the group receiving thoracic epidural analgesia and 45±13% in the control group (P=0.0152); forced expiratory volume in the first second was 56±17% and 41±11%, respectively (P=0.0308). In the pneumonectomy group, 24 hours after the surgery, forced vital capacity was 47±16% in the group receiving thoracic epidural analgesia, 35±8% in the control group (P=0.080). Forced expiratory volume in the first second was 47±15% and 36±7%, respectively (P=0.0449). Conclusion. We conclude that analgesia with intramuscularly administered opioids provides unsatisfactory analgesia, especially in the first days after the operation. Thoracic epidural analgesia is a safe method, which provides a better quality of life for the patient, decreases the postoperative complication rate, and improves the ventilation function after the lung operations.
Bland–Altman analysis as an alternative approach for statistical evaluation of agreement between two methods for measuring hemodynamics during acute myocardial infarction
Authors: Braždžionytė Julija , Macas Andrius
Published: June 2018

Background and objective. Evaluation of hemodynamics in patients with acute myocardial infarction is crucial. In clinical practice, the comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analyzed inappropriately, notably by using correlation coefficients. Our objective is to present an alternative approach, suggested by D. G. Altman and J. M. Bland, based on graphical techniques and simple calculations, for evaluation of the agreement of two methods – intermittent thermodilution (recognized and accepted as a “gold standard” for hemodynamic monitoring) and impedance cardiography (newly introduced method). Patients and methods. A total of 34 patients (20 (58.8%) men and 14 (41.2%) women) were investigated according to the study protocol at Kaunas University of Medicine Hospital. A prospective controlled study was designed to compare two different methods – intermittent thermodilution and impedance cardiography – of cardiac output measurement simultaneously in patients with acute myocardial infarction. Statistical analysis was performed with Bland–Altman and linear regression. Results. A total of 34 paired measurements were carried out in 34 patients at the initiation of hemodynamic monitoring and 30 paired measurements in 32 patients after subsequent improvement or stabilization of clinical status. Correlation coefficient ranged from 0.37 to 0.98. Conclusions. Bland–Altman analysis is an alternative method for assessing the agreement between two methods of clinical measurement. According to our data, noninvasive technique – impedance cardiography – is a reliable method for hemodynamic monitoring in noncomplicated cases of acute myocardial infarction.
Outpatient methadone maintenance treatment program Quality of life and health of opioid-dependent persons in Lithuania
Authors: Padaiga Žilvinas , Subata Emilis , Vanagas Giedrius
Published: June 2018

Background. The evaluation of quality of life and self-perceived health represents an assessment of the impact of treatment on patient functioning and well-being. Objective. Our aim was to explore the impact of methadone maintenance treatment on quality of life and self-perceived health of opioid-dependent persons in Lithuania. Methods. A total of 102 opioid-dependent patients were recruited in the study. A prospective follow-up study design was used. To assess quality of life, the WHOQOL-BREF 26-item version was used. The impact of methadone maintenance treatment on self-perceived health was assessed by Opiate Treatment Index (OTI). Results. Following 6 months of methadone maintenance treatment, significant improvements in physical (P=0.004), psychological (P=0.004), and environmental (P=0.048) components of quality of life were observed; no statistically significant improvements were found in social component of quality of life. Study participants reported lower rates of medical morbidity associated with injection (P<0.001), cardiorespiratory (P=0.034), musculoskeletal (P<0.001), neurological (P=0.013), gastrointestinal (P<0.001), and general health (P<0.001). Conclusions. Methadone maintenance treatment substantially reduces morbidity associated with opioid dependence and improves the quality of life of patients.
Electrical injuries
Authors: Adukauskienė Dalia , Vizgirdaitė Venta , Mažeikienė Sandra
Published: June 2018

Electrical trauma can be caused by low-voltage current (from 60 to 1000 V, usually 220 or 360 V), high-voltage (more than 1000 V) current, lightning, and voltaic arc. Often victims are little children, teenagers, and working-age adults. Electrical injuries and clinical manifestations can vary a lot and range from mild complaints undemanding serious medical help to life-threatening conditions. Lightning causes serious injuries in 1000–1500 individuals every year worldwide. The case fatality rate is about 20–30%, with as many as 74% of survivors experiencing permanent injury and sequela. The primary cause of death in victims of lightning strike or other electrical trauma is cardiac or respiratory arrest. That is why appropriate urgent help is essential. Subsequently electrical burns, deep-tissue and organ damage caused by electricity, secondary systemic disorders often demand intensive care and prompt, usually later multistage surgical treatment; therefore, prevention of electrical trauma, which would help to reduce electrical injuries in children and working-age population, is very actual. The most important is to understand the possible danger of electricity and to avoid it.
Non-Destructive Electrochemical Testing for Stainless-Steel Components with Complex Geometry Using Innovative Gel Electrolytes
Authors: Monrrabal Gleidys , Ramírez-Barat Blanca , Bautista Asunción , Velasco Francisco , Cano Emilio
Published: June 2018

Corrosion can be a problem for stainless steels in chloride-containing or other aggressive environments, especially when they are formed as components with complex shapes. Monitoring the corrosion performance of the stainless steels during their in-service life is not always an easy task. Traditional electrochemical cells can be difficult to adapt to complex surfaces, and undesired crevices or liquid electrolyte leaks can occur. In the presented work, the possible use of non-destructive techniques with innovative gel electrolytes was investigated using portable cells. The electrolytes were based on agar (used as a gelling agent with ionic conductivity), glycerol (a plasticizer that improves adaptability to complex surfaces), and NaCl or KClO4 salts (which improve the conductivity and control the aggression of the tests). X-ray photoelectron spectroscopy (XPS) and Mott–Schottky analysis were carried out to obtain information about the influence of the electrolyte on the passive layer. The oxygen concentration and conductivity in the gels with various glycerol contents were compared to those in liquid electrolytes. Electrochemical impedance spectroscopy (EIS) measurements were carried out in liquids and gels. The performance of the gel cell on a stainless-steel component with a weld and complex shape was checked. The variation in the sensitivity of gels with and without chlorides to identify corrosion-susceptible regions was tested.
Simulation and Experiment on Droplet Formation and Separation for Needle-Type Micro-Liquid Jetting Dispenser
Authors: Lu Shizhou , Cao Guangyu , Zheng Hai , Li Dongqi , Shi Meiyan , Qi Jiahui
Published: June 2018

The needle-type droplet jetting dispenser has wide applications in the field of microelectronic packaging, and for which the good quality of droplet formation and separation is the key to successful dispensing. This paper simulates the droplet jetting process which has been divided into 5 stages named backflow, growth, droplet extension, breakage, and separation, and analyses the combined effects of system parameters, such as pressure, viscosity, needle stroke, and nozzle diameter, on the changes of morphologies of ejected droplets, which is verified by experiments. The simulation and experiment results show that a higher driving pressure is quite suitable for the high-viscosity liquid to form normal droplets by avoiding adhesion. When increasing the needle stroke, the pressure should also be lowered properly to prevent the flow-stream. Besides, the nozzle with a large diameter is much more likely to cause sputtering or satellite-droplet problems. The results have a great significance for guiding the parameter settings of the needle-type dispensing approach.
Effect of Sodium Pyrophosphate on the Reverse Flotation of Dolomite from Apatite
Authors: Chen Yanfei , Feng Qiming , Zhang Guofan , Liu Dezhi , Liu Runzhe
Published: June 2018

In this study, the effect of sodium pyrophosphate (NaPP) on the separation of apatite from dolomite by flotation was systematically investigated. Flotation results revealed that NaPP could selectively depress the flotation of apatite, thus realizing the separation of apatite from dolomite. Further, the selective depression mechanism of NaPP was studied through zeta potential measurements, contact angle measurements, and X-ray photoelectron spectroscopy (XPS) analysis. The results demonstrated that the adsorption of sodium oleate (NaOL) onto apatite surface was depressed by the preferential interaction of NaPP with active Ca sites. For dolomite, while the presence of NaPP hindered the interaction of NaOL with active Ca sites, it appeared to enhance the reactivity with active Mg sites. Thus, the adsorption of NaOL onto dolomite surface was hardly influenced. In this way, the separation of apatite from dolomite was achieved.
Erratum: Borrego-Sánchez, A., et al. Molecular Modeling of Adsorption of 5-Aminosalicylic Acid in the Halloysite Nanotube. Minerals 2018, 8, 61
Authors:   Minerals Editorial Office
Published: June 2018

We would like to change the first one of authors’ affiliations of paper [1] from:[...]
New Bisabosquals from Stachybotrys sp. PH30583 Elicited on Solid Media
Authors: Ruan Bao-Hui , Li Shu-Quan , Yang Xue-Qiong , Yang Ya-Bin , Wu Ya-Mei , Shi Li-Jiao , Yin Hai-Yue , Zhou Hao , Ding Zhong-Tao
Published: June 2018

Stachybotrys sp. PH30583 cultured in liquid medium only led to one structure type of novel isochroman dimers. Using the one strain-many compounds strategy, the reinvestigation of the metabolites from Stachybotrys sp. PH30583 cultured in rice solid medium led to the isolation of four triprenyl phenols, including two new bisabosquals and two known phenylspirodrimanes. Nitrobisabosquals A and B (1 and 2) are the first case of pyrrolidone-bisabosquals reported in literature. Totally different compounds were isolated using rice solid medium, compared with those isolated using liquid medium, so that rice solid medium presents a key factor in the production of triprenyl phenols. Compound 1 exhibited cytotoxicity against tumor cells, A-549, HL-60, MCF-7 SMMC-7721, and SW480, as well as weak anticoagulant activity with activated partial thromboplastin time (APTT) of 32.1 ± 0.17 s (p < 0.05 vs. Con.) at a concentration of 5 mM. Triprenyl phenol metabolites could be used as chemotaxonomic markers for Stachybotrys.
A Pharmacometabolomic Approach to Predict Response to Metformin in Early-Phase Type 2 Diabetes Mellitus Patients
Authors: Park Jeong-Eun , Jeong Gui-Hwa , Lee In-Kyu , Yoon Young-Ran , Liu Kwang-Hyeon , Gu Namyi , Shin Kwang-Hee
Published: June 2018

Metformin is a first-line medication for type 2 diabetes mellitus (T2DM). Based on its universal use, the consideration of inter-individual variability and development of predictive biomarkers are clinically significant. We aimed to identify endogenous markers of metformin responses using a pharmacometabolomic approach. Twenty-nine patients with early-phase T2DM were enrolled and orally administered metformin daily for 6 months. A total of 22 subjects were included in the final analysis. Patients were defined as responders or non-responders based on changes in their glycated haemoglobin A1c (HbA1c) from baseline, over 3 months. Urine metabolites at baseline, as well as at the 3 and 6 month follow-ups after the start of treatment were analysed using gas chromatography-mass spectrometry and evaluated with multivariate analyses. Metabolites distinguishable between the two response groups were obtained at baseline, as well as at the 3 and 6 month follow-ups, and significantly different metabolites were listed as markers of metformin response. Among the identified metabolites, citric acid, myoinositol, and hippuric acid levels showed particularly significant differences between the non-responder and responder groups. We thus identified different metabolite profiles in the two groups of T2DM patients after metformin administration, using pharmacometabolomics. These results might facilitate a better understanding and prediction of metformin response and its variability in individual patients.
Cu(II) Complexes of 4-[(1E)-N-{2-[(Z)-Benzylidene-amino]ethyl}ethanimidoyl]benzene-1,3-diol Schiff Base: Synthesis, Spectroscopic, In-Vitro Antioxidant, Antifungal and Antibacterial Studies
Authors: Ejidike Ikechukwu P.
Published: June 2018

The current study reports the synthesis of copper complexes of a tridentate Schiff base ligand. The compounds of the type [Cu(L)X]∙n(H2O) (where L = tridentate ONN Schiff base ligand, X = Cl−, Br−, SCN−, NO3−, CH3COO−), were characterized on the basis of elemental analyses, FT-IR, UV-vis, molar conductance, 1H-NMR, XRD and thermal analyses. The spectra revealed that the Schiff base ligand acts as a tridentate ligand through two azomethine nitrogen atoms and a phenolic oxygen atom. The molar conductance measurements of the complexes in DMF correspond to non-electrolytic nature. TGA and DTA studies results gave insight into the dehydration, thermal stability, and thermal decomposition. Square-planar geometry has been assigned to the prepared complexes as indicated by the electronic spectral measurements. Cu(II) compounds showed antiradical potential against DPPH and ABTS radicals. The antimicrobial potential of the Schiff base ligand and its Cu(II) complexes were evaluated by the rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay against some selected bacteria strains: Staphylococcus aureus and Enterococcus faecalis (Gram +ve); Klebsiella pneumoniae and Pseudomonas aeruginosa (Gram −ve), and fungi (Candida albicans and Cryptococcus neoformans). The compounds showed a broad spectrum of antibacterial and antifungal activities, with MIC values ranging from 48.83 to 3125 μg/mL.
Triorganoindium Reagents in Rh-Catalyzed C–H Activation/C–C Cross-Coupling Reactions of 2-Arylpyridines
Authors: Riveiros Ricardo , Tato Rubén , Pérez Sestelo José , Sarandeses Luis A.
Published: June 2018

The activation of C–H bonds through catalytic reactions using transition metals is an important challenge in organic chemistry in which the intermediates are related to those produced in the classical cross-coupling reactions. As part of our research program devoted to the development of metal-catalyzed reactions using indium organometallics, a protocol for the C–H activation and C–C coupling of 2-arylpyridines with triorganoindium reagents under Rh(I) catalysis is reported. Under the optimized conditions, we found that Me3In and Ar3In reagents reacted with 2-arylpyridines and related compounds in the presence of Rh(PPh3)3Cl, in PhCl/THF (9:1), at 120 °C for 48 h, to afford the ortho-coupling products in moderate to good yields. The nitrogen atom in the pyridine ring acts as a directing group to assist the functionalization at the ortho position of the aryl group forming a new C–C bond at this position.
Scoring Amino Acid Mutations to Predict Avian-to-Human Transmission of Avian Influenza Viruses
Authors: Qiang Xiaoli , Kou Zheng , Fang Gang , Wang Yanfeng
Published: June 2018

Avian influenza virus (AIV) can directly cross species barriers and infect humans with high fatality. Using machine learning methods, the present paper scores the amino acid mutations and predicts interspecies transmission. Initially, 183 signature positions in 11 viral proteins were screened by the scores of five amino acid factors and their random forest rankings. The most important amino acid factor (Factor 3) and the minimal range of signature positions (50 amino acid residues) were explored by a supporting vector machine (the highest-performing classifier among four tested classifiers). Based on these results, the avian-to-human transmission of AIVs was analyzed and a prediction model was constructed for virology applications. The distributions of human-origin AIVs suggested that three molecular patterns of interspecies transmission emerge in nature. The novel findings of this paper provide important clues for future epidemic surveillance.
The Mechanism for siRNA Transmembrane Assisted by PMAL
Authors: Lu Yanfei , Li Jipeng , Su Nan , Lu Diannan
Published: June 2018

The capacity of silencing genes makes small interfering RNA (siRNA) appealing for curing fatal diseases. However, the naked siRNA is vulnerable to and degraded by endogenous enzymes and is too large and too negatively charged to cross cellular membranes. An effective siRNA carrier, PMAL (poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine), has been demonstrated to be able to assist siRNA transmembrane by both experiments and molecular simulation. In the present work, the mechanism of siRNA transmembrane assisted by PMAL was studied using steered molecular dynamics simulations based on the martini coarse-grained model. Here two pulling rates, i.e., 10−6 and 10−5 nm·ps−1, were chosen to imitate the passive and active transport of siRNA, respectively. Potential of mean force (PMF) and interactions among siRNA, PMAL, and lipid bilayer membrane were calculated to describe the energy change during siRNA transmembrane processes at various conditions. It is shown that PMAL-assisted siRNA delivery is in the mode of passive transport. The PMAL can help siRNA insert into lipid bilayer membrane by lowering the energy barrier caused by siRNA and lipid bilayer membrane. PMAL prefers to remain in the lipid bilayer membrane and release siRNA. The above simulations establish a molecular insight of the interaction between siRNA and PMAL and are helpful for the design and applications of new carriers for siRNA delivery.
Theoretical Characterization by Density Functional Theory (DFT) of Delphinidin 3-O-Sambubioside and Its Esters Obtained by Chemical Lipophilization
Authors: Márquez-Rodríguez Ana , Grajeda-Iglesias Claudia , Sánchez-Bojorge Nora-Aydeé , Figueroa-Espinoza María-Cruz , Rodríguez-Valdez Luz-María , Fuentes-Montero María , Salas Erika
Published: June 2018

Anthocyanins are water-soluble phenolic pigments. However, their poor solubility in lipidic media limits their use. This hurdle can be overcome with the lipophilization of anthocyanins, which consists of adding an aliphatic chain to a hydrophilic compound, in order to increase its solubility in lipids. Still, the unspecific chemical lipophilization of anthocyanin-esters produces molecules with different properties from their precursors. In this work, experimental changes of anthocyanin-esters obtained by chemical lipophilization are investigated in silico aiming specifically at observing their molecular behavior and comparing it with their anthocyanin precursor. Thus, the analysis of delphinidin 3-O-sambubioside and its esters employing Density Functional Theory (DFT) methods, such as the hybrid functional B3LYP in combination with the 6-31++G(d,p) Pople basis set, provides the ground state properties, the local reactivity and the molecular orbitals (MOs) of these compounds. Excited states properties were analyzed by TD-DFT with the B3LYP functional, and the M06 and M06-2X meta-GGA functionals. Local reactivity calculations showed that the electrophilic site for all the anthocyanin-esters was the same as the one for the anthocyanin precursor, however the nucleophilic site changed depending localization of the esterification. TD-DFT results indicate that the place of esterification could change the electronic transitions and the MOs spatial distribution.
Chemical Structures and Biological Activities of Limonoids from the Genus Swietenia (Meliaceae)
Authors: Sun Yun-Peng , Jin Wen-Fang , Wang Yong-Yue , Wang Gang , Morris-Natschke Susan L. , Liu Jin-Song , Wang Guo-Kai , Lee Kuo-Hsiung
Published: June 2018

Swietenia is a genus in the plant family Meliaceae. This genus contains seven to eight known species, found in the tropical and subtropical regions of the Americas and West Africa. Thus far, more than 160 limonoids have been isolated from four species of the genus Swietenia. Limonoids are rich in structure type and biological activity, and these compounds are the main active components in the Swietenia species. This paper will give a comprehensive overview of the recent phytochemical and pharmacological research on the terpenes from Swietenia plants and encourage further drug discovery research.
New Records of Potent In-Vitro Antidiabetic Properties of Dalbergia tonkinensis Heartwood and the Bioactivity-Guided Isolation of Active Compounds
Authors: Nguyen Van Bon , Wang San-Lang , Nhan Ngu Truong , Nguyen Thi Hanh , Nguyen Nguyen Phuong Dai , Nghi Do Huu , Cuong Nguyen Manh
Published: June 2018

Alpha-glucosidase inhibitory activity has been commonly used for the evaluation of antidiabetic property in vitro. The aim of this study is to investigate and characterize Dalbergia tonkinensis as a potential source of antidiabetic compounds. The screening of the active parts used, such as trunk bark, heartwood, and the leaves of Dalbergia tonkinensis indicated that all these extracted parts used with methanol demonstrated potent α-glucosidase inhibitory activity. The in vitro antidiabetic property of Dalbergia tonkinensis was notably recorded for the first time and showed activity (EC50 = 0.17–0.78 mg/mL) comparable to those of reported potent herbal extracts (EC50 = 0.25–4.0 mg/mL) and higher activity than that of acarbose, a commercial antidiabetic drug (EC50 = 1.21 mg/mL). The stability tests revealed that the heartwood of Dalbergia tonkinensis extract (HDT) possesses high pH stability with relative activity in the range of 80–98%. Further bioassay-guided purification led to the isolation of 2 active compounds identified as sativanone and formononetin from the ethyl acetate fraction and water fraction of HDT, respectively. These α-glucosidase inhibitors (aGIs) show promising inhibition against various types of α-glucosidases. Remarkably, these inhibitors were determined as new mammalian aGIs, showing good effect on rat α-glucosidase. The results suggest that Dalbergia tonkinensis is a potent source of aGIs and suggest promise in being developed as functional food with antidiabetic efficacy. The results of this study also enrich our knowledge concerning current biological activity and constituents of Dalbergia tonkinensis species.
Design, Synthesis, and Evaluation of Homochiral Peptides Containing Arginine and Histidine as Molecular Transporters
Authors: El-Sayed Naglaa , Miyake Taryn , Shirazi Amir , Park Shang , Clark Jimmy , Buchholz Stephani , Parang Keykavous , Tiwari Rakesh
Published: June 2018

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 µM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the peptides through the cell membrane. Thus, we synthesized seven fatty acyl derivatives of the linear (HR)4 peptide. The peptides were synthesized using Fmoc/tBu solid phase peptide chemistry, purified by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption/ionization (MALDI) spectrometry. The fatty acyl peptides containing C8, C12, C14, and C18 alkyl chain did not show cytotoxicity on SK-OV-3 or CCRF-CEM cell lines up to 50 µM concentration; however, at higher concentration (100 µM), they showed mild cytotoxicity. For example, C16-(HR)4 was also found to reduce the proliferation of SK-OV-3 cells by 11% at 50 µM and C20-(HR)4 showed mild toxicity at 10 µM, reducing the proliferation of SK-OV-3 cells by 21%. Increase in the length of alkyl chain showed cytotoxicity to the cell lines. C20-(HR)4 peptide showed better efficiency in translocation of F′-GpYEEI to SK-OV-3 than the phosphopeptide alone. Further investigation of C20-(HR)4 peptide efficacy showed that the peptide could deliver doxorubicin and epirubicin into SK-OV-3 and also improved the drug antiproliferative ability. These studies provided insights into understanding the structural requirements for optimal cellular delivery of the fatty acyl-(HR)4 peptide conjugates.
Protein Hydrolysates’ Absorption Characteristics in the Dynamic Small Intestine In Vivo
Authors: He Yuanqing , Shen Lingling , Ma Chaoyue , Chen Min , Pan Ye , Yin Lijing , Zhou Jie , Lei Xiaochun , Ren Qian , Duan Yuqing , Zhang Haihui , Ma Haile
Published: June 2018

Background: Dietary proteins are known for their wide range of nutritional, functional and biological properties. Although the total amount of proteins may be obtained from mixtures, its “availability” for absorption in the gut is in many cases quite uncertain or even varies for the same food depending on processing conditions, the presence of other components, and so on. Methods: To obtain accurate protein hydrolysate absorption data, we have developed a small intestine model (SIM) to test them. Results: The results indicated that the protein hydrolysates were absorbed rapidly during the first 15 min, and then decreased to 90 min, then they were absorbed again from 90 min to the endpoint. The protein absorption was also affected by the protein processing method used. The Enzyme + Ultrasound (EU) processing method group had a higher absorption rate than the Enzyme (E) processing method group, and the absorption of the Enzyme + Artificial gastric juice processing method (EH) and Enzyme + Ultrasound + Artificial gastric juice processing method (EUH) groups was reduced compared to the E group alone. The amino acid analysis results showed that the amino acids were reduced and absorbed by our SIM in almost all groups except for cysteine and methionine. In general, the Pearson relation value of the amino acid contents between before SIM and after SIM was 0.887, which indicated that single amino acid absorption was mainly related to its content in the whole amino acids. The single amino acid absorption ratio among different groups also displayed differences, which ranged from 31% to 46% (E group from 39% to 42%; EU group from 40% to 47%; EH group from 31% to 39%; EUH group from 35% to 41%). Conclusions: The protein hydrolysates’ varied from startpoint to endpoint, and the protein absorption was affected by processing method.
Effectiveness of Essence of Chicken on Cognitive Function Improvement: A Randomized Controlled Clinical Trial
Authors: Suttiwan Panrapee , Yuktanandana Pongsak , Ngamake Sakkaphat
Published: June 2018

High-quality, adequately-powered clinical trials investigating the effect of Essence of Chicken (EC) on cognitive function are lacking. We conducted a randomized, double-blind, placebo-controlled clinical trial on healthy adult volunteers to determine the effect of EC on short-term memory, working memory, and selective and sustained attention. As a secondary objective, we evaluated baseline stress as a modifying factor by including treatment, stress and visit as main effects in a three-way ANOVA model. Cognitive function was evaluated at baseline, and Days 7 and 14. Data from 235 participants were analyzed on a per-protocol basis. The three-way interaction effect was significant (p = 0.020) in Digit Span Forward and further analyses showed EC improved test performance in moderate (p = 0.041) and severe stress (p = 0.065) but not in normal and mild stress subgroups. In Digit Span Backward, EC group showed greater improvement compared to placebo (p = 0.028), with 0.60 digits (8.50% improvement from baseline) more recalled on Day 7. No treatment or interaction effects were statistically significant in selective and sustained attention tests. Our findings support EC’s effect in improving mental processes used in working memory among healthy adults and short-term memory among healthy adults experiencing stress in daily life.
A Framework for the Development of Integrated and Computationally Feasible Models of Large-Scale Mammalian Cell Bioreactors
Authors: Farzan Parham , Ierapetritou Marianthi G.
Published: June 2018

Industrialization of bioreactors has been achieved by applying several core concepts of science and engineering. Modeling has deepened the understanding of biological and physical phenomena. In this paper, the state of existing cell culture models is summarized. A framework for development of dynamic and computationally feasible models that capture the interactions of hydrodynamics and cellular activities is proposed. Operating conditions are described by impeller rotation speed, gas sparging flowrate, and liquid fill level. A set of admissible operating states is defined over discretized process parameters. The burden on a dynamic solver is reduced by assuming hydrodynamics at its fully developed state and implementation of compartmental modeling. A change in the conditions of operation is followed by hydrodynamics switching instantaneously to the steady state that would be reached under new conditions. Finally, coupling the model with optimization solvers leads to improvements in operation.