bluuebunny/crossref_metadata_2025 huggingface dataset:
Network between Cytokines, Cortisol and Occupational Stress in Gas and Oilfield Workers
Authors: Reale Marcella , Costantini Erica , D’Angelo Chiara , Coppeta Luca , Mangifesta Rocco , Jagarlapoodi Srinivas , Di Nicola Marta , Di Giampaolo Luca
Published: February 2020

To test whether gas and oil field work is accompanied by stress and altered immune function, the perception of workplace stress, levels of salivary cortisol, plasma levels, and mononuclear cell production of cytokines were examined in 80 healthy workers recruited among a population of operators on gas and oilfields. Specific questionnaires for determining the perception of anxiety, occupational stress, and subjective symptoms were administered. Salivary cortisol and cytokines plasma levels were evaluated by Elisa and to investigate immune function, both spontaneous and PHA- or LPS-induced expression and production of cytokines were assessed by qRT-PCR. Workers showed medium stress levels at work, with growth and increased motivation for work, and based on salivary cortisol concentrations, were divided into two groups of ≤10 ng/mL (n = 31) or >10 ng/mL (n = 49). Statistically significant higher plasma levels of IL-6, while lower TNFα, were detected in workers with cortisol >10 ng/mL. Also, BMI, DL, JD and Job strain were significantly higher in workers with cortisol >10 ng/mL. Thus, even modest variations of cortisol might have a role in the modulation of immune response and worker’s vulnerability to health imbalance.Thus, the evaluation of immune status, in addition to cortisol levels, could be useful to prevent illnesses; exacerbation of pre-existing conditions; morbidity; and consequent absences from work, with economic repercussions.
Nuclear Argonaute Piwi Gene Mutation Affects rRNA by Inducing rRNA Fragment Accumulation, Antisense Expression, and Defective Processing in Drosophila Ovaries
Authors: Stolyarenko Anastasia D.
Published: February 2020

Drosophila key nuclear piRNA silencing pathway protein Piwi of the Argonaute family has been classically studied as a factor controlling transposable elements and fertility. Piwi has been shown to concentrate in the nucleolus for reasons largely unknown. Ribosomal RNA is the main component of the nucleolus. In this work the effect of a piwi mutation on rRNA is described. This work led to three important conclusions: A mutation in piwi induces antisense 5S rRNA expression, a processing defect of 2S rRNA orthologous to the 3′-end of eukaryotic 5.8S rRNA, and accumulation of fragments of all five rRNAs in Drosophila melanogaster ovaries. Hypotheses to explain these phenomena are proposed, possibly involving the interaction of the components of the piRNA pathway with the RNA surveillance machinery.
RNA-Targeting CRISPR–Cas Systems and Their Applications
Authors: Burmistrz Michal , Krakowski Kamil , Krawczyk-Balska Agata
Published: February 2020

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)–CRISPR-associated (Cas) systems have revolutionized modern molecular biology. Numerous types of these systems have been discovered to date. Many CRISPR–Cas systems have been used as a backbone for the development of potent research tools, with Cas9 being the most widespread. While most of the utilized systems are DNA-targeting, recently more and more attention is being gained by those that target RNA. Their ability to specifically recognize a given RNA sequence in an easily programmable way makes them ideal candidates for developing new research tools. In this review we summarize current knowledge on CRISPR–Cas systems which have been shown to target RNA molecules, that is type III (Csm/Cmr), type VI (Cas13), and type II (Cas9). We also present a list of available technologies based on these systems.
k-Root-n: An Efficient Algorithm for Avoiding Short Term Double-Spending Alongside Distributed Ledger Technologies such as Blockchain
Authors: Schreiber Zvi
Published: February 2020

Blockchains such as the bitcoin blockchain depend on reaching a global consensus on the distributed ledger; therefore, they suffer from well-known scalability problems. This paper proposes an algorithm that avoids double-spending in the short term with just O(√n) messages instead of O(n); each node receiving money off-chain performs the due diligence of consulting k√n random nodes to check if any of them is aware of double-spending. Two nodes receiving double-spent money will in this way consult at least one common node with very high probability, because of the ‘birthday paradox’, and any common honest node consulted will detect the fraud. Since the velocity of money in the real world has coins circulating through at most a few wallets per day, the size of the due diligence communication is small in the short term. This ‘k-root-n’ algorithm is suitable for an environment with synchronous or asynchronous (but with fairly low latency) communication and with Byzantine faults. The presented k-root-n algorithm should be practical to avoid double-spending with arbitrarily high probability, while feasibly coping with the throughput of all world commerce. It is resistant to Sybil attacks even beyond 50% of nodes. In the long term, the k-root-n algorithm is less efficient. Therefore, it should preferably be used as a complement, and not a replacement, to a global distributed ledger technology.
Outcomes of Vitrectomy for Long-Duration Macular Hole
Authors: Lumi Xhevat , Mahnic Mina , Petrovski Beáta Éva , Petrovski Goran
Published: February 2020

The present study investigated the functional and anatomical outcomes of idiopathic chronic macular hole (MH) surgery with different surgical approaches related to the chronicity and diameter of the MH. A comparative retrospective study between three groups of patients who underwent vitrectomy for long-duration MH (mean: 13.5 months) was conducted. In the first group of patients (G1 or IP), the internal limiting membrane (ILM) was systematically peeled; in the second group (G2 or IPEP), the ILM and epiretinal membrane (ERM) were peeled; and in the third group (G3 or IF), patients underwent inverted ILM flap technique surgery. Pre- and post-operative best corrected visual acuities (pre- and post-op BCVA) were studied. Macular optical coherence tomography (OCT) scans were performed to measure the MH minimum and maximum diameter pre-operatively, as well as to confirm its post-op closure and evaluate the integrity of the ellipsoid zone (EZ). Fifty eyes of 48 patients (33 female and 15 male) were retrospectively evaluated. MH closure rate was 100% in IP group, 66.7% in IPEP, and 95.2% in IF group. All three groups had a statistically significant improvement of BCVA. EZ post-op was restored in 88.2% of the cases from G1, 41.6% from G2, and 23.8% from G3. No statistically significant relationship between the smaller or larger MH diameter and the visual acuity improvement was found. Patients with chronic MH and ERM have worse functional and anatomical outcomes after surgery. Treatment of chronic MHs without ERM results in a better closure rate with either an inverted ILM flap approach or systematic ILM peel.
Possible Recycling of Cigarette Butts as Fiber Modifier in Bitumen for Asphalt Concrete
Authors: Rahman Md Tareq , Mohajerani Abbas , Giustozzi Filippo
Published: February 2020

Littering waste is among the top environmental issues in the world, and the management of the waste has turned into a challenge in almost every city. It has been reported that 75% of smokers dispose of their cigarette butts (CBs) on the ground, even in public places. Researchers have discovered that CBs make up more than one-third of the total littered waste on the planet. Cigarette butts predominantly consist of a cellulose acetate fiber (plastic)-based filter wrapped in paper. Waste CBs contain burnt tobacco and tar, along with many other toxic chemicals. They take years to biodegrade depending on the environmental conditions, and toxic chemicals leach out and contaminate the environment. As part of an ongoing project, this paper presents a novel and sustainable technique to recycle cigarette butts in bitumen for the construction of flexible pavements. In this research, CBs have been pre-processed and mixed with bitumen classes C320, C170, and PMB A10E as a fiber modifier. Comprehensive laboratory investigations, including a penetration test, softening point test, and viscosity test, have been performed along with a binder drain off test to evaluate the performance of the modified samples. During this investigation, samples were prepared with 0.3% cellulose fiber, 0.2%, 0.3% 0.4%, and 0.5% CBs. The results of the CB-modified samples were compared with the sample with cellulose fiber and fresh bitumen (0% fiber). The results show that the physical and rheological properties of bitumen incorporating CBs improve significantly, and CBs could be used instead of virgin cellulose fiber as a fiber modifier.
Rotational Compression of Cylindrical Specimen As a New Calibrating Test for Damage Criteria
Authors: Pater Zbigniew , Tomczak Janusz , Bulzak Tomasz , Wójcik Łukasz , Walczuk-Gągała Patrycja
Published: February 2020

The subject-matter of the article is the ductile fracture of materials—A phenomenon occurring in numerous metal forming processes. In order to prognosticate the possibility of a fracture, damage criteria are employed. Their effectiveness, however, depends on the accurate determination of the critical values of damage. These values are obtained through calibrating tests, where the stress state has to be as similar to the actual process as possible. The currently employed calibrating tests do not enable one to determine the limit values of the damage function when the Mannesmann effect occurs. Therefore it was not possible to effectively prognosticate the material fracture in the processes of cross- and skew-rolling. A new calibrating test, based on rotational compression of a cylindrical sample, in which the fractures are caused by the Mannesmann effect, was developed at the Lublin University of Technology. This test was discussed in the article, with a particular focus on the stress and strain state in the sample. A practical use of the test was presented on the example of C45 grade steel, formed in the temperature equal 1150 °C. In the research ten material damage criteria were adopted.
Influence of LWE on Strength of Welded Joints of HSS S960—Experimental and Numerical Analysis
Authors: Dzioba Ihor , Pala Tadeusz
Published: February 2020

This paper presents a strength analysis of joints made during high-strength steel S960 welding. Joints obtained by conventional and laser welding were tested. The most attention was focused on assessing the strength of the material at Heat Affect Zone (HAZ). To this aim, the effect of Linear Welding Energy (LWE) on changes in microstructure and material characteristics was studied. Numerical models of welded joints were developed using the FEM ABAQUS program. The modelled joints were subjected to simulation loads, which allowed to determine areas (the weakest links) of joints in which the destruction process may develop. Good compatibility of the strains fields on the outer surfaces of the joints calculated numerically and recorded by means of the GOM video system was obtained. Based on the tests carried out, it can be concluded that the use of welding with low levels of LEW allow obtaining joints with comparable strength to the base material.
Analysis of the Machining Process of Titanium Ti6Al-4V Parts Manufactured by Wire Arc Additive Manufacturing (WAAM)
Authors: Veiga Fernando , Gil Del Val Alain , Suárez Alfredo , Alonso Unai
Published: February 2020

In the current days, the new range of machine tools allows the production of titanium alloy parts for the aeronautical sector through additive technologies. The quality of the materials produced is being studied extensively by the research community. This new manufacturing paradigm also opens important challenges such as the definition and analysis of the optimal strategies for finishing-oriented machining in this type of part. Researchers in both materials and manufacturing processes are making numerous advances in this field. This article discusses the analysis of the production and subsequent machining in the quality of TI6Al4V produced by Wire Arc Additive Manufacturing (WAAM), more specifically Plasma Arc Welding (PAW). The promising results observed make it a viable alternative to traditional manufacturing methods.
The Application of Submerged Modules for Membrane Distillation
Authors: Gryta Marek
Published: February 2020

This paper deals with the efficiency of capillary modules without an external housing, which were used as submerged modules in the membrane distillation process. The commercial hydrophobic capillary membranes fabricated for the microfiltration process were applied. Several constructional variants of submerged modules were discussed. The influence of membrane arrangement, packing density, capillary diameter and length on the module performance was determined. The effect of process conditions, i.e., velocity and temperature of the streams, on the permeate flux was also evaluated. The submerged modules were located in the feed tank or in the distillate tank. It was found that much higher values of the permeate flux were obtained when the membranes were immersed in the feed with the distillate flowing inside the capillary membranes. The efficiency of submerged modules was additionally compared with the conventional membrane distillation (MD) capillary modules and a similar performance of both constructions was achieved.
Additive Manufacturing of Micromanipulator Mounted on a Glass Capillary for Biological Applications
Authors: Kozaki Shingo , Moritoki Yukihito , Furukawa Taichi , Akieda Hikaru , Kageyama Tatsuto , Fukuda Junji , Maruo Shoji
Published: February 2020

In this study, a three-dimensional (3D) micromanipulator mounted on a glass capillary is developed for handling biological samples, such as multicellular spheroids and embryos. To fabricate the micromanipulator, we developed an additive manufacturing system based on high-resolution microstereolithography using a 405-nm blue laser. The fabrication system makes it possible to fabricate 3D microstructures on a glass capillary with 2.5 µm lateral resolution and 25 µm layer thickness. We also demonstrated the capture and release of a spheroid with the micromanipulator fabricated using our additive manufacturing system. We showed that spheroids can be easily handled by a simple operation with minimal damage using a cage-like multiple finger structure. Additive manufacturing of tailor-made micromanipulators mounted on a glass capillary will be useful in biological and tissue engineering research.
Microspinning: Local Surface Mixing via Rotation of Magnetic Microparticles for Efficient Small-Volume Bioassays
Authors: Kim Su Deok , Song Seo Woo , Oh Dong Yoon , Lee Amos Chungwon , Koo Jeong Woo , Kang Taehun , Kim Min Chang , Lee Changhee , Jeong Yunjin , Jeong Hyun Yong , Lee Daewon , Cho Seongkyu , Kwon Sunghoon , Kim Jiyun
Published: February 2020

The need for high-throughput screening has led to the miniaturization of the reaction volume of the chamber in bioassays. As the reactor gets smaller, surface tension dominates the gravitational or inertial force, and mixing efficiency decreases in small-scale reactions. Because passive mixing by simple diffusion in tens of microliter-scale volumes takes a long time, active mixing is needed. Here, we report an efficient micromixing method using magnetically rotating microparticles with patterned magnetization induced by magnetic nanoparticle chains. Because the microparticles have magnetization patterning due to fabrication with magnetic nanoparticle chains, the microparticles can rotate along the external rotating magnetic field, causing micromixing. We validated the reaction efficiency by comparing this micromixing method with other mixing methods such as simple diffusion and the use of a rocking shaker at various working volumes. This method has the potential to be widely utilized in suspension assay technology as an efficient mixing strategy.
Geological Controls on Mineralogy and Geochemistry of the Permian and Jurassic Coals in the Shanbei Coalfield, Shaanxi Province, North China
Authors: Shangguan Yunfei , Zhuang Xinguo , Li Jing , Li Baoqing , Querol Xavier , Liu Bo , Moreno Natalia , Yuan Wei , Yang Guanghua , Pan Lei
Published: February 2020

Coal as the source of critical elements has attracted much attention and the enrichment mechanisms are of significant importance. This paper has an opportunity to investigate the mineralogical and geochemical characteristics of the Permian and Jurassic bituminous coals and associated non-coals from two underground coal mines in the Shanbei Coalfield (Northeast Ordos basin), Shaanxi Province, North China, based on the analysis of X-ray diffraction (XRD), inductively coupled plasma atomic-emission spectrometry (ICP-AES/MS), and scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS). The Jurassic and Permian coals have similar chemical features excluding ash yield, which is significantly higher in the Permian coals. Major mineral matters in the Jurassic coals are quartz, kaolinite, and calcite. By contrast, mineral assemblages of the Permian coals are dominated by kaolinite; and apatite occurring in the middle section’s partings. The Jurassic coals are only enriched in B, whereas the Permian coals are enriched in some trace elements (e.g., Nb, Ta, Th, and REY). Boron has a mixed inorganic and organic association which may be absorbed by organic matter from fluid (or groundwater) or inherited from coal-forming plants. Additionally, climatic variation also plays an important role. As for the Permian coals, kaolinite and apatite as the major carriers of elevated elements; the former were derived from the sedimentary source region (the Yinshan Oldland and the Benxi formation) and later precipitated from Ca-, and P-rich solutions. We deduced that those elevated elements may be controlled by the source rock and diagenetic fluid input. The findings of this work offered new data to figure out the mechanism of trace element enrichment of coal in the Ordos basin.
Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents
Authors: Yang Yueqin , Vankayalapati Hariprasad , Tang Manshu , Zheng Yingbo , Li Yingri , Ma Cong , Lai Kent
Published: February 2020

To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention. In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance. We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers. Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM. The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively. One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2. Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM. Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells. siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition. Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively. With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
Comparison of an Offline SPE–GC–MS and Online HS–SPME–GC–MS Method for the Analysis of Volatile Terpenoids in Wine
Authors: Williams Cody , Buica Astrid
Published: February 2020

The aroma profile is an important marker for wine quality. Various classes of compounds are responsible for the aroma of wine, and one such class is terpenoids. In the context of this work, a validated gas chromatography–mass spectrometry (GC–MS) method for the quantitation of terpenoids in red and white wine using headspace solid-phase microextraction (HS–SPME) and solid-phase extraction (SPE) was established. Calibrations were performed in the respective base wine using both sample preparation methods. The linearity, precision and accuracy evaluated for the respective matrices were excellent for both sample preparations. However, the HS–SPME approach was more sensitive and more accurate. For both sample preparations, the quantification limits were lower than the odor thresholds in wine. The terpenoid concentrations (µg/L) were evaluated for 13 white wines using both sample preparation methods. Importantly, the online HS–SPME approach was more sensitive than the offline SPE method. The major terpenoids identified in the white wines evaluated were linalool (0.2–63 µg/L), geraniol (nd–66 µg/L) and α-terpineol (nd–85 µg/L).
1,2- and 1,1-Migratory Insertion Reactions of Silylated Germylene Adducts
Authors: Walewska Małgorzata , Baumgartner Judith , Marschner Christoph
Published: February 2020

The reactions of the PMe3 adduct of the silylated germylene [(Me3Si)3Si]2Ge: with GeCl2·dioxane were found to yield 1,1-migratory insertion products of GeCl2 into one or two Ge–Si bonds. In a related reaction, a germylene was inserted with tris(trimethylsilyl)silyl and vinyl substituents into a Ge–Cl bond of GeCl2. This was followed by intramolecular trimethylsilyl chloride elimination to another cyclic germylene PMe3 adduct. The reaction of the GeCl2 mono-insertion product (Me3Si)3SiGe:GeCl2Si(SiMe3)3 with Me3SiC≡CH gave a mixture of alkyne mono- and diinsertion products. While the reaction of a divinylgermylene with GeCl2·dioxane only results in the exchange of the dioxane of GeCl2 against the divinylgermylene as base, the reaction of [(Me3Si)3Si]2Ge: with one GeCl2·dioxane and three phenylacetylenes gives a trivinylated germane with a chlorogermylene attached to one of the vinyl units.
Synthesis of New Series of 2-C-(β-D-glucopyranosyl)-Pyrimidines and Their Evaluation as Inhibitors of Some Glycoenzymes
Authors: Szennyes Eszter , Gyémánt Gyöngyi , Somsák László , Bokor Éva
Published: February 2020

Despite the substantial interest in C-glycosyl heterocycles as mimetics of biologically active native glycans, the appearance of C-glycopyranosyl derivatives of six-membered heterocycles, both in synthetic and biological contexts, is rather scarce. As part of our ongoing research program aimed at preparing hitherto barely known 2-C-glycopyranosyl pyrimidines, the goal of the present study was to synthesize new 5-mono- and multiply substituted derivatives of this compound class. Thus, 2-C-(β-D-glucopyranosyl)-5,6-disubstituted-pyrimidin-4(3H)-ones and 4-amino-2-C-(β-D-glucopyranosyl)-5,6-disubstituted-pyrimidines were prepared by base-mediated cyclocondensations of O-perbenzylated and O-unprotected C-(β-D-glucopyranosyl) formamidine hydrochlorides with methylenemalonic acid derivatives. The 2-C-(β-D-glucopyranosyl)-5-substituted-pyrimidines were obtained from the same amidine precursors upon treatment with vinamidinium salts. The deprotected derivatives of these pyrimidines were tested as inhibitors of some glycoenzymes. None of them showed inhibitory activity towards glycogen phosphorylase and α- and β-glucosidase enzymes, but some members of the sets exhibited moderate inhibition against bovine liver β-galactosidase.
New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures
Authors: Tateishi-Karimata Hisae , Ohyama Tatsuya , Muraoka Takahiro , Tanaka Shigenori , Kinbara Kazushi , Sugimoto Naoki
Published: February 2020

Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-π interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure.
Microwave Assisted Reactions of Azaheterocycles Formedicinal Chemistry Applications
Authors: Amariucai-Mantu Dorina , Mangalagiu Violeta , Danac Ramona , Mangalagiu Ionel I.
Published: February 2020

Microwave (MW) assisted reactions have became a powerful tool in azaheterocycles chemistry during the last decades. Five and six membered ring azaheterocycles are privileged scaffolds in modern medicinal chemistry possessing a large variety of biological activity. This review is focused on the recent relevant advances in the MW assisted reactions applied to azaheterocyclic derivatives and their medicinal chemistry applications from the last five years. The review is divided according to the main series of azaheterocycles, more precisely 5- and 6-membered ring azaheterocycles (with one, two, and more heteroatoms) and their fused analogues. In each case, the reaction pathways, the advantages of using MW, and considerations concerning biological activity of the obtained products were briefly presented.
Microencapsulation of Anthocyanin Extracted from Purple Flesh Cultivated Potatoes by Spray Drying and Its Effects on In Vitro Gastrointestinal Digestion
Authors: Vergara Cristina , Pino María Teresa , Zamora Olga , Parada Javier , Pérez Ricardo , Uribe Marco , Kalazich Julio
Published: February 2020

Purple flesh cultivated potato (PP) is a foodstuff scarcely cultivated in the world but with high potential because of its anthocyanin content. Moreover, it has been little explored as a source of anthocyanins (AT) for further applications in formulated food products. The main goal of this research was to study the effect of maltodextrin (MD) and spray drying conditions on the encapsulation efficiency (EE) and bioaccesibility of AT from purple flesh cultivated potato extract (PPE). The anthocyanin-rich extract was obtained from PP and microencapsulated by spray-drying, using MD as the encapsulating agent. A statistical optimization approach was used to obtain optimal microencapsulation conditions. The PPE microparticles obtained under optimal conditions showed 86% of EE. The protector effect of microencapsulation on AT was observed to be stable during storage and in vitro digestion. The AT degradation rate constant was significantly lower for the PPE-MD than for the PPE. The assessed bioaccesibility of AT from the PPE-MD was 20% higher than that of the PPE, which could be explained by the protective effect of encapsulation against environmental conditions. In conclusion, microencapsulation is an effective strategy to protect AT from PP, suggesting that AT may be an alternative as a stable colorant for use in the food industry.
GPR6 Structural Insights: Homology Model Construction and Docking Studies
Authors: Isawi Israa H. , Morales Paula , Sotudeh Noori , Hurst Dow P. , Lynch Diane L. , Reggio Patricia H.
Published: February 2020

GPR6 is an orphan G protein-coupled receptor that has been associated with the cannabinoid family because of its recognition of a sub-set of cannabinoid ligands. The high abundance of GPR6 in the central nervous system, along with high constitutive activity and a link to several neurodegenerative diseases make GPR6 a promising biological target. In fact, diverse research groups have demonstrated that GPR6 represents a possible target for the treatment of neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Several patents have claimed the use of a wide range of pyrazine derivatives as GPR6 inverse agonists for the treatment of Parkinson’s disease symptoms and other dyskinesia syndromes. However, the full pharmacological importance of GPR6 has not yet been fully explored due to the lack of high potency, readily available ligands targeting GPR6. The long-term goal of the present study is to develop such ligands. In this paper, we describe our initial steps towards this goal. A human GPR6 homology model was constructed using a suite of computational techniques. This model permitted the identification of unique GPR6 structural features and the exploration of the GPR6 binding crevice. A subset of patented pyrazine analogs were docked in the resultant GPR6 inactive state model to validate the model, rationalize the structure-activity relationships from the reported patents and identify the key residues in the binding crevice for ligand recognition. We will take this structural knowledge into the next phase of GPR6 project, in which scaffold hopping will be used to design new GPR6 ligands.
Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties
Authors: Wosińska-Hrydczuk Marzena , Boratyński Przemysław J. , Skarżewski Jacek
Published: February 2020

In this report, we describe the synthetic elaboration of the easily available enantiomerically pure β-amino alcohols. Attempted direct substitution of the hydroxyl group by azido-functionality in the Mitsunobu reaction with hydrazoic acid was inefficient or led to a diastereomeric mixture. These outcomes resulted from the participation of aziridines. Intentionally performed internal Mitsunobu reaction of β-amino alcohols gave eight chiral aziridines in 45–82% yield. The structural and configuration identity of products was confirmed by NMR data compared to the DFT calculated GIAO values. For 1,2,3-trisubstituted aziridines slow configurational inversion at the endocyclic nitrogen atom was observed by NMR at room temperature. Moreover, when aziridine was titrated with Zn(OAc)2 under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN3 to form the corresponding azido amines as single regio- and diastereomers in 90–97% yield. Different results were obtained for 1,2-disubstituted and 1,2,3-trisubstituted aziridines. For the later aziridines ring closure and ring opening occurred at different carbon stereocenters, thus yielding products with two inverted configurations, compared to the starting amino alcohol. The 1,2-disubstituted aziridines produced azido amines of the same configuration as the starting β-amino alcohols. To obtain a complete series of diastereomeric vic-diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in SN2 reaction (25–58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral vic-diamines of defined stereochemistries.
Impact of Perovskite Composition on Film Formation Quality and Photophysical Properties for Flexible Perovskite Solar Cells
Authors: Li Guangdong , Zou Xiaoping , Cheng Jin , Chen Dan , Yao Yujun , Chang Chuangchuang , Yu Xing , Zhou Zixiao , Wang Junqi , Liu Baoyu
Published: February 2020

In recent years, flexible perovskite solar cells have drawn tremendous attention in the field of wearable devices, and optimization of perovskite composition plays an important role in improving film quality and photophysical properties. At present, some researchers have only studied A-site organic cations mixing or X-site halide anions mixing in the ABX3 structure of perovskite, but there are few reports on co-mixing of A-site and X-site ions in flexible perovskite solar cells. In this paper, we mainly try to study the effects of different concentrations of mixed formamidine methylamine halide (FAxMA1-xBrxClyI1-x-y) precursor solutions on the quality and photophysical properties of perovskite films under low temperature process. We conclude that the film quality and photophysical properties reached the best results when the optimized precursor solution concentration was 60:6:6. The investigation on composition optimization in this experiment laid the foundation for the improvement of the performance of flexible perovskite solar cells. We also use the results of this experiment to prepare flexible perovskite solar cells based on carbon electrodes, which are expected to be applied in other flexible optoelectronic or electro-optical devices.
Flavonoids as Novel Efflux Pump Inhibitors and Antimicrobials Against Both Environmental and Pathogenic Intracellular Mycobacterial Species
Authors: Solnier Julia , Martin Liam , Bhakta Sanjib , Bucar Franz
Published: February 2020

Therapeutic treatment options for opportunistic non-tuberculous mycobacterial (NTM) infection and/or serious mycobacterial infections such as tuberculosis (TB) and leprosy are limited due to the spread of antimicrobial resistance mechanism. Plant-derived natural compounds as prospective efflux pump inhibitors may present a promising adjunct to conventional chemotherapy by enhancing mycobacterial susceptibility to antibiotics. This study served to evaluate the antimicrobial and resistance-modifying profile of a range of plant-derived flavonoids against the mycobacterial model strains: M. smegmatis, M. aurum, and M. bovis BCG. The minimum inhibitory concentrations (MICs) of the compounds against the mycobacterial strains were determined using both agar dilution and broth dilution assays, while their efflux inhibitory activity was investigated via an ethidium bromide-based fluorometric assay. All compounds were screened for their synergistic effects with ethidium bromide (EtBr) and rifampicin (RIF) against M. smegmatis. Skullcapflavone II (5,2′-dihydroxy-6,7,8,6′-tetramethoxyflavone, 1) exerted potent antimicrobial activity against M. aurum and M. bovis BCG and considerably increased the susceptibility of M. smegmatis to EtBr and RIF. Nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone, 2) was determined to be the most potent efflux-inhibitor in M. aurum and M. smegmatis. However, a connection between strong modulatory and putative efflux activity of the compounds could not be observed. Nevertheless, the results highlight two polymethoxyflavones, skullcapflavone II and nobiletin, with potent antimycobacterial and antibiotic resistance modulating activities as valuable adjuvants in anti-mycobacterial therapies.
Nanodroplets of Docosahexaenoic Acid-Enriched Algae Oil Encapsulated within Microparticles of Hydrocolloids by Emulsion Electrospraying Assisted by Pressurized Gas
Authors: Prieto Cristina , Lagaron Jose M.
Published: February 2020

Long chain polyunsaturated omega-3 fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important functional ingredients due to their well-documented health benefits, but highly susceptible to oxidation. One of the most promising approaches to preserve bioactives is their encapsulation within protective matrices. In this paper, an innovative high throughput encapsulation technique termed as emulsion electrospraying assisted by pressurized gas (EAPG) was used to encapsulate at room temperature nanodroplets of algae oil into two food hydrocolloids, whey protein concentrate and maltodextrin. Spherical encapsulating particles with sizes around 5 µm were obtained, where the oil was homogeneously distributed in nanometric cavities with sizes below 300 nm. Peroxide values under 5 meq/kg, demonstrated that the oil did not suffer from oxidation during the encapsulation process carried out at room temperature. An accelerated stability assay against oxidation under strong UV light was performed to check the protective capacity of the different encapsulating materials. While particles made from whey protein concentrate showed good oxidative stability, particles made from maltodextrin were more susceptible to secondary oxidation, as determined by a methodology put forward in this study based on ATR-FTIR spectroscopy. Further organoleptic testing performed with the encapsulates in a model food product, i.e., milk powder, suggested that the lowest organoleptic impact was seen for the encapsulates made from whey protein concentrate. The obtained results demonstrate the potential of the EAPG technology using whey protein concentrate as the encapsulating matrix, for the stabilization of sensitive bioactive compounds.
Effect of Compressive Prestrain on the Anti-Pressure and Anti-Wear Performance of Monolayer MoS2: A Molecular Dynamics Study
Authors: Kong Ning , Wei Boyu , Zhuang Yuan , Zhang Jie , Li Hongbo , Wang Bo
Published: February 2020

The effects of in-plane prestrain on the anti-pressure and anti-wear performance of monolayer MoS2 have been investigated by molecular dynamics simulation. The results show that monolayer MoS2 observably improves the load bearing capacity of Pt substrate. The friction reduction effect depends on the deformation degree of monolayer MoS2. The anti-pressure performance of monolayer MoS2 and Pt substrate is enhanced by around 55.02% when compressive prestrain increases by 4.03% and the anti-wear performance is notably improved as well. The improved capacities for resisting the in-plane tensile and out-of-plane compressive deformation are responsible for the outstanding lubrication mechanism of monolayer MoS2. This study provides guidelines for optimizing the anti-pressure and anti-wear performance of MoS2 and other two-dimension materials which are subjected to the in-plane prestrain.
Removal of Diclofenac, Paracetamol, and Carbamazepine from Model Aqueous Solutions by Magnetic Sol–Gel Encapsulated Horseradish Peroxidase and Lignin Peroxidase Composites
Authors: Pylypchuk Ievgen V. , Daniel Geoffrey , Kessler Vadim G. , Seisenbaeva Gulaim A.
Published: February 2020

Sustainable and green synthesis of nanocomposites for degradation of pharmaceuticals was developed via immobilization and stabilization of the biological strong oxidizing agents, peroxidase enzymes, on a solid support. Sol–gel encapsulated enzyme composites were characterized using electron microscopy (TEM, SEM), atomic force microscopy, FTIR spectroscopy, and thermogravimetric analysis. Horseradish peroxidase (HRP) and lignin peroxidase (LiP) were adsorbed onto magnetite nanoparticles and sol–gel encapsulated in a surface silica layer. Encapsulation enhanced the stability of the biocatalysts over time and thermal stability. The biocatalysts showed appreciable selectivity in oxidation of the organic drinking water pollutants diclofenac, carbamazepine, and paracetamol with improved activity being pharmaceutical specific for each enzyme. In particular, sol–gel encapsulated LiP- and HRP-based nanocomposites were active over 20 consecutive cycles for 20 days at 55 °C (24 h/cycle). The stability of the sol–gel encapsulated catalysts in acidic medium was also improved compared to native enzymes. Carbamazepine and diclofenac were degraded to 68% and 64% by sol–gel LiP composites respectively at pH 5 under elevated temperature. Total destruction of carbamazepine and diclofenac was achieved at pH 3 (55 °C) within 3 days, in the case of both immobilized HRP and LiP. Using NMR spectroscopy, characterization of the drug decomposition products, and decomposition pathways by the peroxidase enzymes suggested.
Ultrasound- and Microbubble-Assisted Gemcitabine Delivery to Pancreatic Cancer Cells
Authors: Bjånes Tormod , Kotopoulis Spiros , Murvold Elisa Thodesen , Kamčeva Tina , Gjertsen Bjørn Tore , Gilja Odd Helge , Schjøtt Jan , Riedel Bettina , McCormack Emmet
Published: February 2020

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death worldwide. Poor drug delivery to tumours is thought to limit chemotherapeutic treatment efficacy. Sonoporation combines ultrasound (US) and microbubbles to increase the permeability of cell membranes. We assessed gemcitabine uptake combined with sonoporation in vitro in three PDAC cell lines (BxPC-3, MIA PaCa-2 and PANC-1). Cells were cultured in hypoxic bioreactors, while gemcitabine incubation ± sonoporation was conducted in cells with operational or inhibited nucleoside membrane transporters. Intracellular active metabolite (dFdCTP), extracellular gemcitabine, and inactive metabolite (dFdU) concentrations were measured with liquid chromatography tandem mass spectrometry. Sonoporation with increasing US intensities resulted in decreasing extracellular gemcitabine concentrations in all three cell lines with inhibited membrane transporters. In cells with inhibited membrane transporters, without sonoporation, dFdCTP concentrations were reduced down to 10% of baseline. Sonoporation partially restored gemcitabine uptake in these cells, as indicated by a moderate increase in dFdCTP concentrations (up to 37% of baseline) in MIA PaCa-2 and PANC-1. In BxPC-3, gemcitabine was effectively inactivated to dFdU, which might represent a protective mechanism against dFdCTP accumulation in these cells. Intracellular dFdCTP concentrations did not change significantly following sonoporation in any of the cell lines with operational membrane transporters, indicating that the gemcitabine activation pathway may have been saturated with the drug. Sonoporation allowed a moderate increase in gemcitabine transmembrane uptake in all three cell lines, but pre-existing nucleoside transporters were the major determinants of gemcitabine uptake and retention.
Larch Wood Residues Valorization through Extraction and Utilization of High Value-Added Products
Authors: Wagner Kerstin , Musso Maurizio , Kain Stefan , Willför Stefan , Petutschnigg Alexander , Schnabel Thomas
Published: February 2020

Many of current bio-based materials are not fully or partly used for material utilization, as the composition of their raw materials and/or possible applications are unknown. This study deals with the analysis of the wood extractives from three different tissue of larch wood: Sapwood mainly from outer part of the log, and sound knotwood as well as dead knotwood. The extractions were performed with an accelerated solvent extractor (ASE) using hexane and acetone/water. The obtained extracts were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Three various vibrational spectroscopy (FT-RAMAN, FT-IR and FT-NIR) methods reflect the information from the extracts to the chemical composition of the types of wood before the extraction processes. Multivariate data analysis of the spectra was used to obtain a better insight into possible classification methods. Taxifolin and kaempferol were found in larger amount in sound knotwood samples compared to larch wood with high percentage of sapwood and dead knotwood samples. While the extractions of dead knotwood samples yielded more larixol and resin acids than the other larch wood samples used. Based on the chemical composition, three lead compounds were defined for the classification of the different wood raw materials. The vibrational spectroscopy methods were applied to show their potential for a possible distinction of the three types of larch wood tissue. This new insight into the different larch wood extracts will help in the current efforts to use more environmentally friendly raw materials for innovative applications. The connection between the raw materials and extraction yields of the target values is important to transform the results from the laboratory to industry and consumer applications.
Physico-Chemical Characterization and Biological Tests of Collagen/Silk Fibroin/Chitosan Scaffolds Cross-Linked by Dialdehyde Starch
Authors: Grabska-Zielińska Sylwia , Sionkowska Alina , Reczyńska Katarzyna , Pamuła Elżbieta
Published: February 2020

In this study, three-dimensional (3D) biopolymeric scaffolds made from collagen, silk fibroin and chitosan were successfully prepared by the freeze drying method. Dialdehyde starch (DAS) was used as a cross-linking agent for the materials. The properties of the materials were studied using density and porosity measurements, scanning electron microscope (SEM) imaging, swelling and moisture content measurements. Additionally, cytocompatibility of the materials in contact with MG-63 osteoblast-like cells was tested by live/dead staining and resazurin reduction assay on days 1, 3 and 7. It was found that new 3D materials made from collagen/silk fibroin/chitosan binary or ternary mixtures are hydrophilic with a high swelling ability (swelling rate in the range of 1680–1900%). Cross-linking of such biopolymeric materials with DAS increased swelling rate up to about 2100%, reduced porosity from 96–97% to 91–93%, and also decreased density and moisture content of the materials. Interestingly, presence of DAS did not influence the microstructure of the scaffolds as compared to non-cross-linked samples as shown by SEM. All the tested samples were found to be cytocompatible and supported adhesion and growth of MG-63 cells as shown by live–dead staining and metabolic activity test.
Simulation of Hydraulic Fracturing Using Different Mesh Types Based on Zero Thickness Cohesive Element
Authors: Chen Minwei , Li Min , Wu Yanzeng , Kang Boqi
Published: February 2020

Hydraulic fracturing is a significant technique in petroleum engineering to enhance the production of shale gas or shale oil reservoir. The process of hydraulic fracturing is extremely complicated, referring to the deformation of solid formation, fluid flowing in the crack channel, and coupling the solid with fluid. Simulation of hydraulic fracturing and understanding the course of the mechanism is still a challenging task. In this study, two hydraulic fracturing models, including the Khristianovic–Geertsma–de Klerk (KGD) problem and the hydraulic fracture (HF) intersection with the natural fracture (NF), based on the zero thickness pore pressure cohesive zone (PPCZ) element with contact friction is established. The element can be embedded into the edges of other elements to simulate the fracture initiation and propagation. However, the mesh type of the elements near the PPCZ element has influences on the accuracy and propagation profile. Three common types of mesh, triangle mesh, quadrangle mesh, and deformed quadrangle mesh, are all investigated in this paper. In addition, the infinite boundary condition (IBC) is also discussed in these models. Simulation indicates that the results of pore pressure for zero toughness regime simulated by the triangle mesh are much lower than any others at the early injection time. Secondly, the problem of hydraulic fracturing should be better used with the infinite boundary element (IBE). Moreover, suggestions for crack intersection on the proper mesh type are also given. The conclusions included in this article can be beneficial to research further naturally fractured reservoirs.