bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact Toughness Anisotropy of TA31 Titanium Alloy Cylindrical Shell after Ring Rolling
Authors: Jiang Haiyang , Zhang Jianyang , Xie Bijun , He Zhangxun , Zhang Hao , Wang Bing , Xu Bin , Wu Yuxi , Sun Mingyue
Published: September 2020

The impact toughness of a TA31 titanium alloy cylindrical shell was investigated systemically after ring rolling. The impact toughness of specimens with different notch orientations shows obvious anisotropy. The microstructure of the cylindrical shell and the impact fracture were characterized by an optical microscope and scanning electron microscope. The results show that cracks are easier to propagate in the equiaxed α phase than the elongated α phase. This is because the expanding cracking path in the equiaxed α phase is shorter than that in the elongated α phase, and thereby the cracks are easier to propagate in the equiaxed α phase than the elongated α phase. More specifically, the α phase on the RD-TD plane was obviously isotropic, which makes it easy for the cracks to propagate along α grains in the same direction. However, the α phase on the RD-ND plane has a layered characteristic, and the direction of the α phase varies from layer to layer, thus it requires higher energy for cracks to propagate across this layered α phase. Therefore, the cracks propagating in the same α phase orientation take easier than that in the layered α phase, so it has lower impact toughness.
LC-MS/MS Method Development for the Discovery and Identification of Amphidinols Produced by Amphidinium
Authors: Wellkamp Marvin , García-Camacho Francisco , Durán-Riveroll Lorena M. , Tebben Jan , Tillmann Urban , Krock Bernd
Published: September 2020

Amphidinols are polyketides produced by dinoflagellates suspected of causing fish kills. Here, we demonstrate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the identification and quantification of amphidinols (AM). Novel AM were detected by neutral loss (NL) scan and then quantified together with known AM by selection reaction monitoring (SRM). With the new method, AM were detected in four of eight analyzed strains with a maximum of 3680 fg toxin content per cell. In total, sixteen novel AM were detected by NL scan and characterized via their fragmentation patterns. Of these, two substances are glycosylated forms. This is the first detection of glycosylated AM.
8-(Pyridin-2-yl)quinolin-7-ol as a Platform for Conjugated Proton Cranes: A DFT Structural Design
Authors: Georgiev Anton , Antonov Liudmil
Published: September 2020

Theoretical design of conjugated proton cranes, based on 7-hydroxyquinoline as a tautomeric sub-unit, has been attempted by using ground and excited state density functional theory (DFT) calculations in various environments. The proton crane action request existence of a single enol tautomer in ground state, which under excitation goes to the excited keto tautomer through a series of consecutive excited-state intramolecular proton transfer (ESIPT) steps with the participation of the crane sub-unit. A series of substituted pyridines was used as crane sub-units and the corresponding donor-acceptor interactions were evaluated. The results suggest that the introduction of strong electron donor substituents in the pyridine ring creates optimal conditions for 8-(pyridin-2-yl)quinolin-7-ols to act as proton cranes.
Fabrication of Tapered 3D Microstructure Arrays Using Dual-Exposure Lithography (DEL)
Authors: Rengarajan Venkatakrishnan , Geng Junnan , Huang Yu
Published: September 2020

Three-dimensional (3D) microstructure arrays (MSAs) have been widely used in material science and biomedical applications by providing superhydrophobic surfaces, cell-interactive topography, and optical diffraction. These properties are tunable through the engineering of microstructure shapes, dimensions, tapering, and aspect ratios. However, the current fabrication methods are often too complex, expensive, or low-throughput. Here, we present a cost-effective approach to fabricating tapered 3D MSAs using dual-exposure lithography (DEL) and soft lithography. DEL used a strip-patterned film mask to expose the SU-8 photoresist twice. The mask was re-oriented between exposures (90° or 45°), forming an array of dual-exposed areas. The intensity distribution from both exposures overlapped and created an array of 3D overcut micro-pockets in the unexposed regions. These micro-pockets were replicated to DEL-MSAs in polydimethylsiloxane (PDMS). The shape and dimension of DEL-MSAs were tuned by varying the DEL parameters (e.g., exposure energy, inter-exposure wait time, and the photomask re-orientation angle). Further, we characterized various properties of our DEL-MSAs and studied the impact of their shape and dimension. All DEL-MSAs showed optical diffraction capability and increased hydrophobicity compared to plain PDMS surface. The hydrophobicity and diffraction angles were tunable based on the MSA shape and aspect ratio. Among the five MSAs fabricated, the two tallest DEL-MSAs demonstrated superhydrophobicity (contact angles >150°). Further, these tallest structures also demonstrated patterning proteins (with ~6–7 μm resolution), and mammalian cells, through microcontact printing and direct culturing, respectively. Our DEL method is simple, scalable, and cost-effective to fabricate structure-tunable microstructures for anti-wetting, optical-, and bio-applications.
Molecular Survey and Genetic Diversity of Hemoplasmas in Rodents from Chile
Authors: Alabí Amir Salvador , Monti Gustavo , Otth Carola , Sepulveda-García Paulina , Sánchez-Hidalgo Melissa , de Mello Victória Valente Califre , Machado Rosangela Zacarias , André Marcos Rogério , Bittencourt Pedro , Müller Ananda
Published: September 2020

Even though hemotrophic mycoplasma (hemoplasma) infections are well documented in a wide variety of hosts worldwide, there is a gap in the knowledge aobut hemoplasmas in rodents. This study aimed to molecularly survey and investigate the genetic diversity of hemoplasmas in rodents from Chile. Synanthropic and wild rodents (n = 74) were captured in the southern province of Valdivia (Corral, Valdivia, Riñihue, and Reumén localities). Spleen samples were submitted to a conventional PCR for hemotrophic Mycoplasma spp. targeting the 16S rRNA gene (800 bp), followed by sequencing, phylogenetic, and genetic diversity analyses. The overall occurrence of hemotrophic mycoplasmas in rodents from Valdivia was 24.5% (18/74) [95% CI (14.5; 34.1)]. Hemoplasmas were detected in Mus musculus (1/4), Rattus norvegicus (1/16), Abrothrix longipilis (7/13), A. olivaceo (6/8), and Oligoryzomys longicaudatus (3/10). The nucleotide polymorphism analysis of the targeted 16S rRNA region showed low diversity, with two genotypes and a high identity to the variants detected in wild rodents from Brazil. Hemoplasmas are described for the first time in rodents from Chile with a moderate occurrence and low 16S rDNA genetic diversity within the sampled rodent population. The detected hemoplasma genotypes were specific to rodents and were not shared with other mammals.
Evolving Profile of HPV-Driven Oropharyngeal Squamous Cell Carcinoma in a National Cancer Institute in Italy: A 10-Year Retrospective Study
Authors: Donà Maria Gabriella , Rollo Francesca , Pichi Barbara , Spriano Giuseppe , Moretto Silvia , Covello Renato , Pellini Raul , Benevolo Maria
Published: September 2020

Globally, 30% of oropharyngeal carcinomas (OPSCC) are caused by Human Papillomavirus (HPV). Recently, increasing incidence trends for HPV-driven OPSCC have been reported in many countries and changes in the typical HPV-positive OPSCC patient have been recorded, with an increase in the median age and diagnoses in women. We investigated the characteristics of the OPSCC patients attending an Italian Cancer Institute from 2010 to 2019 and assessed possible changes overtime of demographic, behavioral, and clinico-pathologic variables of HPV-driven OPSCC. Overall, 339 OPSCCs were evaluated. HPV-DNA and p16 positivity were 48.7% and 55.2%, respectively, with an HPV-driven fraction (i.e., HPV-DNA+/p16+) of 48.3%. We observed a significant increase overtime in the rate of HPV-associated cases (53.7% in 2015–2019 vs. 40.3% in 2010–2014, p = 0.019). The rate of HPV-driven cases was significantly higher among women, never smokers, patients with T1–T2 tumors, and with nodal involvement. A trend was also observed toward an increase in HPV-driven OPSCCs among patients >61 years, women, former smokers, and patients with no nodal involvement in 2015–2019. Our findings consolidate the observation that HPV-associated OPSCCs are also increasing in Italy. Moreover, they suggest that the profile of the HPV-driven OPSCC patient might be changing.
Defects, Diffusion and Dopants in Sillimanite
Authors: Sukumar Raveena , Iyngaran Poobalasuntharam , Kuganathan Navaratnarajah , Chroneos Alexander
Published: September 2020

Aluminum silicate based mineral “Sillimanite” (Al2SiO5) is important in the industrial preparation of aluminum-silicon alloys and cement. In the present study classical pair potential simulations are used to examine the intrinsic defect processes, diffusion pathways of Al3+ and O2− ions together with their activation energies and promising dopants on the Al and Si sites in Al2SiO5. The cation anti-site (Al-Si) defect cluster is calculated to be the most favorable defect, highlighting the cation disorder in this material, in agreement with the experiment. The cation disorder is important as this defect can change the mechanical and chemical properties of Al2SiO5. The Al3+ ions and O2− ions migrate in the c direction with corresponding activation energies of 2.26 eV and 2.75 eV inferring slow ion diffusion. The prominent isovalent dopants on the Al and Si sites are found to be the Ga and Ge, respectively, suggesting that they can be used to prevent phase transformation and tune the properties of sillimanite.
Polyunsaturated Fatty Acids of Both the Omega-3 and the Omega-6 Family Abrogate the Cytokine-Induced Upregulation of miR-29a-3p by Endothelial Cells
Authors: Maucher Daniel , Schmidt Birte , Kuhlmann Kevin , Schumann Julia
Published: September 2020

Cellular processes fundamentally depend on protein expression control. At this, protein expression is regulated on the transcriptional and the post-transcriptional level. PUFAs are already known to affect gene transcription. The present study was conducted to answer the question whether PUFAs are also able to impact on the miRNA-mediated post-transcriptional fine-tuning of mRNA copy numbers. To this end, cellular miRNA profiles were screened by means of next-generation sequencing and NanoString analysis to compare PUFA-enriched to unsupplemented endothelial cells exposed to an inflammatory milieu. Validation took place by droplet digital PCR, allowing for an absolute quantification of RNA copy numbers. The analyses revealed that the stimulation-induced upregulation of miR-29a-3p is blocked by PUFA enrichment of endothelial cells. What is more, mRNA copy numbers of miR-29a-3p targets, namely the coagulation factors PAI-1, TF, and vWF, as well as the proinflammatory cytokines IL-1β, IL-6, and IL-8, were reduced in PUFA-enriched endothelial cells compared to unsupplemented cells, counteracting the stimulatory effect of an inflammatory environment. These data hint toward a new mechanism of action by which PUFAs modulate the functionality of endothelial cells. Apparently, the inflammation-modulating properties of PUFAs are also mediated at the post-transcriptional level.
Synthesis of Biogenic Gold Nanoparticles from Terminalia mantaly Extracts and the Evaluation of Their In Vitro Cytotoxic Effects in Cancer Cells
Authors: Majoumouo Michele S. , Sharma Jyoti R. , Sibuyi Nicole R. S. , Tincho Marius B. , Boyom Fabrice F. , Meyer Mervin
Published: September 2020

Scientists have demonstrated the potential of plant materials as ‘green’ reducing and stabilizing agents for the synthesis of gold nanoparticles (AuNPs) and opened new ecofriendly horizons to develop effective and less harmful treatment strategies. The current study demonstrated the use of Terminalia mantaly (TM) extracts to synthesize AuNPs with enhanced cytotoxic effects. The TM-AuNPs were synthesized at 25 and 70 °C using water (WTM) and methanolic (MTM) extracts of the leaf, root and stem/bark parts of the plant. The TM-AuNPs were characterized using UV–visible spectrophotometry, dynamic light scattering (DLS), transmission electron microscopy, energy dispersive X-ray (EDX), selection area electron diffraction (SAED) and Fourier transform infrared (FTIR) spectroscopy. Majority of the TM-AuNPs were spherical with a mean diameter between 22.5 and 43 nm and were also crystalline in nature. The cytotoxic effects of TM-AuNPs were investigated in cancer (Caco-2, MCF-7 and HepG2) and non-cancer (KMST-6) cell lines using the MTT assay. While the plant extracts showed some cytotoxicity towards the cancer cells, some of the TM-AuNPs were even more toxic to the cells. The IC50 values (concentrations of the AuNPs that inhibited 50% cell growth) as low as 0.18 µg/mL were found for TM-AuNPs synthesized using the root extract of the plant. Moreover, some of the TM-AuNPs demonstrated selective toxicity towards specific cancer cell types. The study demonstrates the potential of TM extracts to produce AuNPs and describe the optimal conditions for AuNPs using TM extracts. The toxicity of some the TM-AuNPs can possibly be explored in the future as an antitumor treatment.
Synthesis and Properties of CurNQ for the Theranostic Application in Ovarian Cancer Intervention
Authors: Freidus Lara G. , Kumar Pradeep , Marimuthu Thashree , Pradeep Priyamvada , Pillay Viness , Choonara Yahya E.
Published: September 2020

Synthesis of a novel theranostic molecule for targeted cancer intervention. A reaction between curcumin and lawsone was carried out to yield the novel curcumin naphthoquinone (CurNQ) molecule (2,2′-((((1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl) bis(2-methoxy-4,1-phenylene))bis(oxy))bis(naphthalene-1,4-dione). CurNQ’s structure was elucidated and was fully characterized. CurNQ was demonstrated to have pH specific solubility, its saturation solubility increased from 11.15 µM at pH 7.4 to 20.7 µM at pH 6.8. This pH responsivity allows for cancer targeting (Warburg effect). Moreover, CurNQ displayed intrinsic fluorescence, thus enabling imaging and detection applications. In vitro cytotoxicity assays demonstrated the chemotherapeutic properties of CurNQ as CurNQ reduced cell viability to below 50% in OVCAR-5 and SKOV3 ovarian cancer cell lines. CurNQ is a novel theranostic molecule for potential targeted cancer detection and treatment.
Drug Administration Routes Impact the Metabolism of a Synthetic Cannabinoid in the Zebrafish Larvae Model
Authors: Park Yu Mi , Meyer Markus R. , Müller Rolf , Herrmann Jennifer
Published: September 2020

Zebrafish (Danio rerio) larvae have gained attention as a valid model to study in vivo drug metabolism and to predict human metabolism. The microinjection of compounds, oligonucleotides, or pathogens into zebrafish embryos at an early developmental stage is a well-established technique. Here, we investigated the metabolism of zebrafish larvae after microinjection of methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7′N-5F-ADB) as a representative of recently introduced synthetic cannabinoids. Results were compared to human urine data and data from the in vitro HepaRG model and the metabolic pathway of 7′N-5F-ADB were reconstructed. Out of 27 metabolites detected in human urine samples, 19 and 15 metabolites were present in zebrafish larvae and HepaRG cells, respectively. The route of administration to zebrafish larvae had a major impact and we found a high number of metabolites when 7′N-5F-ADB was microinjected into the caudal vein, heart ventricle, or hindbrain. We further studied the spatial distribution of the parent compound and its metabolites by mass spectrometry imaging (MSI) of treated zebrafish larvae to demonstrate the discrepancy in metabolite profiles among larvae exposed through different administration routes. In conclusion, zebrafish larvae represent a superb model for studying drug metabolism, and when combined with MSI, the optimal administration route can be determined based on in vivo drug distribution.
Adsorption Study of Lignin Removal from Recycled Alkali Black Liquor by Adsorption Resins for Improved Cellulase Hydrolysis of Corn Straw
Authors: Li Yiming , Fang Shuo , Zhou Xia , Zhao Zhezhen , Li Fei , Liu Ping
Published: September 2020

Previous studies showed that aromatic compounds such as lignin, phenols, and furans were main inhibitors of cellulase hydrolysis in recycled alkali black liquor (RBL), which should be removed to improve alkali utilization. In this study, three polymeric resins, XAD-4, XAD-16N, and XAD-7HP, were evaluated for their abilities to remove lignin from alkali black liquor recycled at the third time. Adsorption conditions of adsorbent dose and equilibrium time, isotherms, and kinetics were investigated. Of three tested adsorbents, XAD-16N was the most efficient, which can remove 89.84% of lignin after adsorption at an adsorbent-to-solution ratio of 1:4 for 2.5 h. Pseudo-second-order model was efficient to represent XAD-16N and XAD-7HP adsorption kinetics. Adsorption behavior of XAD-4 on RBL was fitted better to Langmuir model, while XAD-16N and XAD-7HP adsorption were more consistent with Freundlich model. The cellulase hydrolysis rate of corn straw treated with RBL after XAD-16N adsorption combined with ozone was 86.89%, which was only 0.89% lower than that of sodium hydroxide combined with ozone treatment. Structure characterization proved that the damage of XAD-16N adsorbed RBL to corn straw was similar to that of sodium hydroxide. It indicated that adsorption was effective in inhibitor removal from RBL to improve alkali utilization.
Synthesis of Naphthoquinone Derivatives: Menaquinones, Lipoquinones and Other Vitamin K Derivatives
Authors: Braasch-Turi Margaret , Crans Debbie C.
Published: September 2020

Menaquinones are a class of isoprenoid molecules that have important roles in human biology and bacterial electron transport, and multiple methods have been developed for their synthesis. These compounds consist of a methylnaphthoquinone (MK) unit and an isoprene side chain, such as found in vitamin K1 (phylloquinone), K2, and other lipoquinones. The most common naturally occurring menaquinones contain multiple isoprene units and are very hydrophobic, rendering it difficult to evaluate the biological activity of these compounds in aqueous assays. One way to overcome this challenge has been the application of truncated MK-derivatives for their moderate solubility in water. The synthesis of such derivatives has been dominated by Friedel-Crafts alkylation with BF3∙OEt2. This attractive method occurs over two steps from commercially available starting materials, but it generally produces low yields and a mixture of isomers. In this review, we summarize reported syntheses of both truncated and naturally occurring MK-derivatives that encompass five different synthetic strategies: Nucleophilic ring methods, metal-mediated reactions, electrophilic ring methods, pericyclic reactions, and homologation and side chain extensions. The advantages and disadvantages of each method are discussed, identifying methods with a focus on high yields, regioselectivity, and stereochemistry leading to a detailed overview of the reported chemistry available for preparation of these compounds.
Current Evidence on the Bioavailability of Food Bioactive Peptides
Authors: Amigo Lourdes , Hernández-Ledesma Blanca
Published: September 2020

Food protein-derived bioactive peptides are recognized as valuable ingredients of functional foods and/or nutraceuticals to promote health and reduce the risk of chronic diseases. However, although peptides have been demonstrated to exert multiple benefits by biochemical assays, cell culture, and animal models, the ability to translate the new findings into practical or commercial uses remains delayed. This fact is mainly due to the lack of correlation of in vitro findings with in vivo functions of peptides because of their low bioavailability. Once ingested, peptides need to resist the action of digestive enzymes during their transit through the gastrointestinal tract and cross the intestinal epithelial barrier to reach the target organs in an intact and active form to exert their health-promoting properties. Thus, for a better understanding of the in vivo physiological effects of food bioactive peptides, extensive research studies on their gastrointestinal stability and transport are needed. This review summarizes the most current evidence on those factors affecting the digestive and absorptive processes of food bioactive peptides, the recently designed models mimicking the gastrointestinal environment, as well as the novel strategies developed and currently applied to enhance the absorption and bioavailability of peptides.
Suppression of Electric Field-Induced Segregation in Sky-Blue Perovskite Light-Emitting Electrochemical Cells
Authors: Liashenko Tatiana G. , Pushkarev Anatoly P. , Naujokaitis Arnas , Pakštas Vidas , Franckevičius Marius , Zakhidov Anvar A. , Makarov Sergey V.
Published: September 2020

Inexpensive perovskite light-emitting devices fabricated by a simple wet chemical approach have recently demonstrated very prospective characteristics such as narrowband emission, low turn-on bias, high brightness, and high external quantum efficiency of electroluminescence, and have presented a good alternative to well-established technology of epitaxially grown III-V semiconducting alloys. Engineering of highly efficient perovskite light-emitting devices emitting green, red, and near-infrared light has been demonstrated in numerous reports and has faced no major fundamental limitations. On the contrary, the devices emitting blue light, in particular, based on 3D mixed-halide perovskites, suffer from electric field-induced phase separation (segregation). This crystal lattice defect-mediated phenomenon results in an undesirable color change of electroluminescence. Here we report a novel approach towards the suppression of the segregation in single-layer perovskite light-emitting electrochemical cells. Co-crystallization of direct band gap CsPb(Cl,Br)3 and indirect band gap Cs4Pb(Cl,Br)6 phases in the presence of poly(ethylene oxide) during a thin film deposition affords passivation of surface defect states and an increase in the density of photoexcited charge carriers in CsPb(Cl,Br)3 grains. Furthermore, the hexahalide phase prevents the dissociation of the emissive grains in the strong electric field during the device operation. Entirely resistant to 5.7 × 106 V·m−1 electric field-driven segregation light-emitting electrochemical cell exhibits stable emission at wavelength 479 nm with maximum external quantum efficiency 0.7%, maximum brightness 47 cd·m−2, and turn-on bias of 2.5 V.
One Dimensional ZnO Nanostructures: Growth and Chemical Sensing Performances
Authors: Moumen Abderrahim , Kaur Navpreet , Poli Nicola , Zappa Dario , Comini Elisabetta
Published: September 2020

Recently, one-dimensional (1D) nanostructures have attracted the scientific community attention as sensitive materials for conductometric chemical sensors. However, finding facile and low-cost techniques for their production, controlling the morphology and the aspect ratio of these nanostructures is still challenging. In this study, we report the vapor-liquid-solid (VLS) synthesis of one dimensional (1D) zinc oxide (ZnO) nanorods (NRs) and nanowires (NWs) by using different metal catalysts and their impact on the performances of conductometric chemical sensors. In VLS mechanism, catalysts are of great interest due to their role in the nucleation and the crystallization of 1D nanostructures. Here, Au, Pt, Ag and Cu nanoparticles (NPs) were used to grow 1D ZnO. Depending on catalyst nature, different morphology, geometry, size and nanowires/nanorods abundance were established. The mechanism leading to the VLS growth of 1D ZnO nanostructures and the transition from nanorods to nanowires have been interpreted. The formation of ZnO crystals exhibiting a hexagonal crystal structure was confirmed by X-ray diffraction (XRD) and ZnO composition was identified using transmission electron microscopy (TEM) mapping. The chemical sensing characteristics showed that 1D ZnO has good and fast response, good stability and selectivity. ZnO (Au) showed the best performances towards hydrogen (H2). At the optimal working temperature of 350 °C, the measured response towards 500 ppm of H2 was 300 for ZnO NWs and 50 for ZnO NRs. Moreover, a good selectivity to hydrogen was demonstrated over CO, acetone and ethanol.
Effects of Zn-Doped Mesoporous Bioactive Glass Nanoparticles in Etch-and-Rinse Adhesive on the Microtensile Bond Strength
Authors: Choi Yeonju , Sun Woogyeong , Kim Yeon , Kim In-Ryoung , Gong Mi-Kyung , Yoon Seog-Young , Bae Moon-Kyoung , Park Bong-Soo , Park Soo-Byung , Kim Yong-Il
Published: September 2020

The purpose of this study was to assess the effects in the dentin bond strength of dental adhesives (DAs) and biological effects using zinc (Zn)-doped mesoporous bioactive glass nanoparticles (MBN-Zn). Synthesized MBN and MBN-Zn were characterized by scanning electron microscopy (SEM), X-ray diffraction and the Brunauer, Emmett and Teller (BET) method. The matrix metalloproteinases (MMP) inhibition effects of DA-MBN and DA-MBN-Zn were analyzed. The microtensile bond strength (MTBS) test was conducted before and after thermocycling to investigate the effects of MBN and MBN-Zn on the MTBS of DAs. The biological properties of DA-MBN and DA-MBN-Zn were analyzed with human dental pulp stem cells (hDPSCs). Compared with the DA, only the DA-1.0% MBN and DA-1.0% MBN-Zn exhibited a statistically significant decrease in MMP activity. The MTBS values after thermocycling were significantly increased in DA-1.0% MBN and DA-1.0% MBN-Zn compared with the DA (p < 0.05). It was confirmed via the MTT assay that there was no cytotoxicity for hDPSCs at 50% extract. In addition, significant increases in the alkaline phosphatase activity and Alizarin Red S staining were observed only in DA-1.0%MBN-Zn. These data suggest the 1.0% MBN and 1.0% MBN-Zn enhance the remineralization capability of DAs and stabilize the long-term MTBS of DAs by inhibiting MMPs.
Recent Advances in Nanomedicine for the Diagnosis and Therapy of Liver Fibrosis
Authors: Bai Xue , Su Gaoxing , Zhai Shumei
Published: September 2020

Liver fibrosis, a reversible pathological process of inflammation and fiber deposition caused by chronic liver injury and can cause severe health complications, including liver failure, liver cirrhosis, and liver cancer. Traditional diagnostic methods and drug-based therapy have several limitations, such as lack of precision and inadequate therapeutic efficiency. As a medical application of nanotechnology, nanomedicine exhibits great potential for liver fibrosis diagnosis and therapy. Nanomedicine enhances imaging contrast and improves tissue penetration and cellular internalization; it simultaneously achieves targeted drug delivery, combined therapy, as well as diagnosis and therapy (i.e., theranostics). In this review, recent designs and development efforts of nanomedicine systems for the diagnosis, therapy, and theranostics of liver fibrosis are introduced. Relative to traditional methods, these nanomedicine systems generally demonstrate significant improvement in liver fibrosis treatment. Perspectives and challenges related to these nanomedicine systems translated from laboratory to clinical use are also discussed.
The GReat-Child TrialTM: A Quasi-Experimental Dietary Intervention among Overweight and Obese Children
Authors: Koo Hui Chin , Poh Bee Koon , Talib Ruzita Abd.
Published: September 2020

Diet composition is a key determinant of childhood obesity. While whole grains and micronutrients are known to decrease the risk of obesity, there are no interventions originating from Southeast Asia that emphasize whole grain as a strategy to improve overall quality of diet in combating childhood obesity. The GReat-Child Trial aimed to improve whole grain intake and quality of diet among overweight and obese children. It is a quasi-experimental intervention based on Social Cognitive Theory. It has a 12-week intervention and 6-month follow-up, consisting of three components that address environmental, personal, and behavioral factors. The intervention consists of: (1) six 30 min lessons on nutrition, using the Malaysian Food Pyramid to emphasize healthy eating, (2) daily deliveries of wholegrain foods to schools so that children can experience and accept wholegrain foods, and (3) diet counseling to parents to increase availability of wholegrain foods at home. Two primary schools with similar demographics in Kuala Lumpur were assigned as control (CG) and intervention (IG) groups. Inclusion criteria were: (1) children aged 9 to 11 years who were overweight/obese; (2) who did not consume whole grain foods; and (3) who had no serious co-morbidity problems. The entire trial was completed by 63 children (31 IG; 32 CG). Study outcomes were measured at baseline and at two time points post intervention (at the 3rd [T1] and 9th [T2] months). IG demonstrated significantly higher intakes of whole grain (mean difference = 9.94, 95%CI: 7.13, 12.75, p < 0.001), fiber (mean difference = 3.07, 95% CI: 1.40, 4.73, p = 0.001), calcium (mean difference = 130.27, 95%CI: 74.15, 186.39, p < 0.001), thiamin (mean difference = 58.71, 95%CI: 26.15, 91.28, p = 0.001), riboflavin (mean difference = 0.84, 95%CI: 0.37, 1.32, p = 0.001), niacin (mean difference = 0.35, 95%CI: 1.91, 5.16, p < 0.001), and vitamin C (mean difference = 58.71, 95%CI: 26.15, 91.28, p = 0.001) compared to CG in T1, after adjusting for covariates. However, T1 results were not sustained in T2 when intervention had been discontinued. The findings indicate that intervention emphasizing whole grains improved overall short-term but not long-term dietary intake among schoolchildren. We hope the present trial will lead to adoption of policies to increase whole grain consumption among Malaysian schoolchildren.
Plasma Lipidomics Reveals Insights into Anti-Obesity Effect of Chrysanthemum morifolium Ramat Leaves and Its Constituent Luteolin in High-Fat Diet-Induced Dyslipidemic Mice
Authors: Shon Jong Cheol , Kim Won Cheol , Ryu Ri , Wu Zhexue , Seo Jong-Su , Choi Myung-Sook , Liu Kwang-Hyeon
Published: September 2020

The Chrysanthemum morifolium Ramat (CM) is widely used as a traditional medicine and herbal tea by the Asian population for its health benefits related to obesity. However, compared to the flowers of CM, detailed mechanisms underlying the beneficial effects of its leaves on obesity and dyslipidemia have not yet been elucidated. Therefore, to investigate the lipidomic biomarkers responsible for the pharmacological effects of CM leaf extract (CLE) in plasma of mice fed a high-fat diet (HFD), the plasma of mice fed a normal diet (ND), HFD, HFD plus CLE 1.5% diet, and HFD plus luteolin 0.003% diet (LU) for 16 weeks were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate analysis. In our analysis, the ND, HFD, CLE, and LU groups were clearly differentiated by partial least-squares discriminant analysis (PLS-DA) score plots. The major metabolites contributing to this differentiation were cholesteryl esters (CEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), ceramides (CERs), and sphingomyelins (SMs). The levels of plasma CEs, LPCs, PCs, SMs, and CERs were significantly increased in the HFD group compared to those in the ND group, and levels of these lipids recovered to normal after administration of CLE or LU. Furthermore, changes in hepatic mRNA expression levels involved in the Kennedy pathway and sphingolipid biosynthesis were also suppressed by treatment with CLE or LU. In conclusion, this study examined the beneficial effects of CLE and LU on obesity and dyslipidemia, which were demonstrated as reduced synthesis of lipotoxic intermediates. These results may provide valuable insights towards evaluating the therapeutic effects of CLE and LU and understanding obesity-related diseases.
Nutritional Management and Biochemical Outcomes during the Immediate Phase after Liver Transplant for Methylmalonic Acidemia
Authors: Siegel Casey , Arnon Ronen , Florman Sander , Bucuvalas John , Oishi Kimihiko
Published: September 2020

Methylmalonic acidemia (MMA) is caused by a deficiency of methyl-malonyl-CoA mutase. It is a multisystemic condition with poor clinical outcomes characterized by frequent metabolic decompensation with acidosis, hyperammonemia and encephalopathy. Restriction of intact protein and supplementation with amino acid-based formula play an important role in its management. Recently, liver transplant (LT) became a treatment option for MMA patients. However, there has been no current consensus on the post-operative nutrition management for MMA patients undergoing transplant, particularly during the initial phase of recovery period with catabolic stressors. We performed a retrospective analysis of clinical and nutritional management as well as biochemical profiles before and after LT in five patients with MMA. Through this study, we observed significant improvement of MMA-associated metabolites after LT. MMA patients were able to tolerate increased intact protein intake post-operatively. At least 1–1.5 g/kg/day of total protein during the acute phase after transplant may be tolerated without worsening of the metabolite levels. This information provides a guide in how to nutritionally manage MMA after LT.
Metabolic Defects Caused by High-Fat Diet Modify Disease Risk through Inflammatory and Amyloidogenic Pathways in a Mouse Model of Alzheimer’s Disease
Authors: Reilly Austin M. , Tsai Andy P. , Lin Peter B. , Ericsson Aaron C. , Oblak Adrian L. , Ren Hongxia
Published: September 2020

High-fat diet (HFD) has been shown to accelerate Alzheimer’s disease (AD) pathology, but the exact molecular and cellular mechanisms remain incompletely understood. Moreover, it is unknown whether AD mice are more susceptible to HFD-induced metabolic dysfunctions. To address these questions, we used 5xFAD mice as an Alzheimer’s disease model to study the physiological and molecular underpinning between HFD-induced metabolic defects and AD pathology. We systematically profiled the metabolic parameters, the gut microbiome composition, and hippocampal gene expression in 5xFAD and wild type (WT) mice fed normal chow diet and HFD. HFD feeding impaired energy metabolism in male 5xFAD mice, leading to increased locomotor activity, energy expenditure, and food intake. 5xFAD mice on HFD had elevated circulating lipids and worsened glucose intolerance. HFD caused profound changes in gut microbiome compositions, though no difference between genotype was detected. We measured hippocampal mRNAs related to AD neuropathology and neuroinflammation and showed that HFD elevated the expression of apoptotic, microglial, and amyloidogenic genes in 5xFAD mice. Pathway analysis revealed that differentially regulated genes were involved in insulin signaling, cytokine signaling, cellular stress, and neurotransmission. Collectively, our results showed that 5xFAD mice were more susceptible to HFD-induced metabolic dysregulation and suggest that targeting metabolic dysfunctions can ameliorate AD symptoms via effects on insulin signaling and neuroinflammation in the hippocampus.
Supramolecular Complexes of β-Cyclodextrin with Clomipramine and Doxepin: Effect of the Ring Substituent and Component of Drugs on Their Inclusion Topologies and Structural Flexibilities
Authors: Aree Thammarat
Published: September 2020

Depression is a global threat. Tricyclic antidepressants (TCAs) are still efficacious in treating depression, albeit with more side effects. Cyclodextrins (CDs) with a suitable nanocavity are potential drug carriers and can enhance the drug bioavailability. Aiming for an atomistic understanding of the CD encapsulation facilitating the improvement of drug stability and the reduction of side effects, a comprehensive study series of the β-CD–TCA inclusion complexes through single crystal X-ray diffraction and density functional theory (DFT) calculation was undertaken. This work reports the supramolecular complexes of β-CD with two pivotal TCAs, clomipramine (CPM; 1) and doxepin (DXP; 2). The different inclusion topologies of the β-CD–TCA complexes were notable. X-ray analysis revealed that, in 1, the CPM B-ring (without chloro group) was entrapped in the β-CD cavity, whereas, in 2, the E-DXP A-ring and the Z-DXP B-ring were disordered in the cavity, yielding energetically favorable complexes primarily maintained by intermolecular C–H⋯π interactions, as indicated by DFT calculation. Because both wings of TCAs were similar, an alternative inclusion scenario of the A-ring was evidenced crystallographically in four other TCA complexes. The enhanced TCA thermodynamic stabilities via CD inclusion complexation helped to reduce the side effects and to increase the bioavailability. Moreover, the scrutinization of six TCAs in different lattice circumstances revealed the greater TCA structural flexibilities for their optimum pharmacological activity while binding with proteins.
Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements
Authors: Hattab Dima , Bakhtiar Athirah
Published: September 2020

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer. Owing to the absenteeism of hormonal receptors expressed at the cancerous breast cells, hormonal therapies and other medications targeting human epidermal growth factor receptor 2 (HER2) are ineffective in TNBC patients, making traditional chemotherapeutic agents the only current appropriate regimen. Patients’ predisposition to relapse and metastasis, chemotherapeutics’ cytotoxicity and resistance and poor prognosis of TNBC necessitates researchers to investigate different novel-targeted therapeutics. The role of small interfering RNA (siRNA) in silencing the genes/proteins that are aberrantly overexpressed in carcinoma cells showed great potential as part of TNBC therapeutic regimen. However, targeting specificity, siRNA stability, and delivery efficiency cause challenges in the progression of this application clinically. Nanotechnology was highlighted as a promising approach for encapsulating and transporting siRNA with high efficiency-low toxicity profile. Advances in preclinical and clinical studies utilizing engineered siRNA-loaded nanotherapeutics for treatment of TNBC were discussed. Specific and selective targeting of diverse signaling molecules/pathways at the level of tumor proliferation and cell cycle, tumor invasion and metastasis, angiogenesis and tumor microenvironment, and chemotherapeutics’ resistance demonstrated greater activity via integration of siRNA-complexed nanoparticles.
Regulation of Sulfate Uptake and Assimilation in Barley (Hordeum vulgare) as Affected by Rhizospheric and Atmospheric Sulfur Nutrition
Authors: Ausma Ties , De Kok Luit J.
Published: September 2020

To study the regulation of sulfate metabolism in barley (Hordeum vulgare), seedlings were exposed to atmospheric hydrogen sulfide (H2S) in the presence and absence of a sulfate supply. Sulfate deprivation reduced shoot and root biomass production by 60% and 70%, respectively, and it affected the plant’s mineral nutrient composition. It resulted in a 5.7- and 2.9-fold increased shoot and root molybdenum content, respectively, and a decreased content of several other mineral nutrients. Particularly, it decreased shoot and root total sulfur contents by 60% and 70%, respectively. These decreases could be ascribed to decreased sulfate contents. Sulfate deficiency was additionally characterized by significantly lowered cysteine, glutathione and soluble protein levels, enhanced dry matter, nitrate and free amino acid contents, an increased APS reductase (APR) activity and an increased expression and activity of the root sulfate uptake transporters. When sulfate-deprived barley was exposed to 0.6 µL L−1 atmospheric H2S, the decrease in biomass production and the development of other sulfur deficiency symptoms were alleviated. Clearly, barley could use H2S, absorbed by the foliage, as a sulfur source for growth. H2S fumigation of both sulfate-deprived and sulfate-sufficient plants downregulated APR activity as well as the expression and activity of the sulfate uptake transporters. Evidently, barley switched from rhizospheric sulfate to atmospheric H2S as sulfur source. Though this indicates that sulfate utilization in barley is controlled by signals originating in the shoot, the signal transduction pathway involved in the shoot-to-root regulation must be further elucidated.
Salt-Tolerant Phenomena, Sequencing and Characterization of a Glyoxalase I (Jojo-Gly I) Gene from Jojoba in Comparison with Other Glyoxalase I Genes
Authors: Mohasseb Heba Allah A. , Solliman Mohei El-Din , Al-Mssallem Ibrahim S. , Abdullah Mohammed M. Ba , Alsaqufi Ahmed Saud , Shehata Wael F. , El-Shemy Hany A.
Published: September 2020

Plant response to salt stress and the mechanism of salt tolerance have received major focus by plant biology researchers. Biotic stresses cause extensive losses in agricultural production globally, but abiotic stress causes significant increase in the methylglyoxal (MG) level of GlyoxalaseI (Gly I). Identification of salt-tolerant genes when characterizing their phenotypes will help to identify novel genes using polymerase chain reaction (PCR) to amplify the DNA coding region for glyoxalase I. This method is specific, requiring only genomic DNA and two pairs of PCR primers, and involving two successive PCR reactions. This method was used rapidly and easily identified glyoxalase I sequences as salt-tolerant genes from Jojoba (Simmondsia chinensis (Link) Schneider). In the present study, the glyoxalase I gene was isolated, amplified by PCR using gene-specific primers and sequenced from the jojoba plant, then compared with other glyoxalase I sequences in other plants and glyoxalase I genes like in Brassica napus, ID: KT720495.1; Brassica juncea ID: Y13239.1, Arachis hypogaea; ID: DQ989209.2; and Arabidopsis thaliana L, ID: AAL84986. The structural gene of glyoxalase I, when sequenced and analyzed, revealed that the uninterrupted open reading frame (ORF) of jojoba Gly I (Jojo-Gly I) spans 775 bp, corresponding to 185 amino acid residues, and shares 45.2% amino acid sequence identity to jojoba (Jojo-Gly I). The cloned ORF, in a multicopy constitutive expression plasmid, complemented the Jojo-Gly I, confirming that the encoded Jojo-Gly I in jojoba showed some homology with other known glyoxalase I sequences of plants.
Chemotaxonomic Evaluation by Volatolomics Analysis of Fifty-Two Genotypes of Myrtus communis L.
Authors: Usai Marianna , Marchetti Mauro , Culeddu Nicola , Mulas Maurizio
Published: September 2020

A population of 52 genotypes of Myrtle (Myrtus communis L.), selected in the framework of a domestication program and growing in the same collection field at Oristano (Central Western Sardinia, 39°54′ N 8°35′ E), was analyzed by GC/MS for leaf essential oil composition. The chemical composition of essential oils was quite variable with a number of compounds ranging from 31 to 78 depending on cultivar. One hundred and eighteen compounds were globally identified in the various genotypes. However, α-pinene, limonene, 1,8-cineole, α-terpineol, and linalool always resulted as main components with few differences among samples. Minor compounds have been the determining factors in differentiating or associating genotypes in the outputs of a principal component analysis (PCA), where the results of another analysis of fruit essential oils of the same genotypes were also jointly used. Genotypes were discriminated according to mother plant characterization or ecological variables, such as site altitude, soil nature, and presence or absence of calcareous soils in the substrate of the localities of origin.
Using Thermally Crosslinkable Hole Transporting Layer to Improve Interface Characteristics for Perovskite CsPbBr3 Quantum-Dot Light-Emitting Diodes
Authors: Lin Chun-Cheng , Yeh Shao-Yang , Huang Wei-Lun , Xu You-Xun , Huang Yan-Siang , Yeh Tzu-Hung , Tien Ching-Ho , Chen Lung-Chien , Tseng Zong-Liang
Published: September 2020

In this paper, a thermally crosslinkable 9,9-Bis[4-[(4-ethenylphenyl)methoxy]phenyl]-N2,N7-di-1-naphthalenyl-N2,N7-diphenyl-9H-fluorene-2,7-diamine (VB-FNPD) film served as the hole transporting layer (HTL) of perovskite CsPbBr3 quantum-dot light-emitting diodes (QD-LEDs) was investigated and reported. The VB-FNPD film crosslinked at various temperatures in the range of 100~230 °C followed by a spin-coating process to improve their chemical bonds in an attempt to resist the erosion from the organic solvent in the remaining fabrication process. It is shown that the device with VB-FNPD HTL crosslinking at 170 °C has the highest luminance of 7702 cd/m2, the maximum current density (J) of 41.98 mA/cm2, the maximum current efficiency (CE) of 5.45 Cd/A, and the maximum external quantum efficiency (EQE) of 1.64%. Our results confirm that the proposed thermally crosslinkable VB-FNPD is a candidate for the HTL of QD-LEDs.
Dimensional Accuracy of Dental Casting Patterns Fabricated Using Consumer 3D Printers
Authors: Ishida Yoshiki , Miura Daisuke , Miyasaka Taira , Shinya Akikazu
Published: September 2020

Consumer 3D printers have improved considerably due to the evolution of additive manufacturing. This study aimed to examine the accuracy of consumer printers in dental restoration. Cylindrical patterns mimicking a full crown were created and enlarged from 100% to 105% of the original size. Two types of consumer 3D printers, including a fused deposition modeling (FDM) device and a stereolithography (SLA) device, and two types of dental 3D printers, including a multi-jet device and an SLA device, were used to fabricate the patterns. Then, the outer and inner diameters and depths, and surface roughness of the patterns were measured. The changing rates of the outer diameter of models created using dental printers were significantly smaller than those of the models created using consumer printers (p < 0.05). Significantly greater surface roughness was obtained in the tooth axis of the model fabricated using the consumer FDM device (p < 0.05). However, no significant differences were observed on the surface roughness of both axes between the consumer SLA device and the dental devices (p > 0.05). However, FDM showed larger surface roughness than dental devices in both axes (p < 0.05). Thus, the SLA consumer printer can be applied to fabricate resin patterns with enlargement editing of 1–3% along the horizontal axis.
Reassessing the Inculcation of an Anti-Racist Ethic for Christian Ministry: From Racism Awareness to Deconstructing Whiteness
Authors: Reddie Anthony
Published: September 2020

This paper outlines the means by which candidates training for Christian ministry are encouraged to engage with the deontological positionality of anti-racism as a substantive element of Christian praxis. The first part of the paper provides some brief historical reflections on what was then the conventional approach to teaching an anti-racist ethic for Christian ministry, namely, the practice of “racism awareness”. Following these reflections, the author proceeds to outline the epistemological change that has occurred in his own ethical teaching, moving from the focus on racism awareness to a more critical, postcolonial deconstruction of Whiteness and its concomitant links to Mission Christianity. Mission Christianity, the religion that underpinned the British Empire, is identified as the repository that helped to institutionalise the existence of “white supremacy” and racism within the body politic of colonialism and the rise of notions of “manifest destiny”. In switching the modus operandi for an anti-racist ethic within Christian ministry, this paper seeks to reframe the ways in which the ethical basis for opposing and resisting racism is effected within Christian theology