bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Consequences of the SCN5A-p.Y1977N Mutation within the PY Ubiquitylation Motif: Discrepancy between HEK293 Cells and Transgenic Mice
Authors: Casini Simona , Albesa Maxime , Wang Zizun , Portero Vincent , Ross-Kaschitza Daniela , Rougier Jean-Sébastien , Marchal Gerard A. , Chung Wendy K. , Bezzina Connie R. , Abriel Hugues , Remme Carol Ann
Published: October 2019

Dysfunction of the cardiac sodium channel Nav1.5 (encoded by the SCN5A gene) is associated with arrhythmias and sudden cardiac death. SCN5A mutations associated with long QT syndrome type 3 (LQT3) lead to enhanced late sodium current and consequent action potential (AP) prolongation. Internalization and degradation of Nav1.5 is regulated by ubiquitylation, a post-translational mechanism that involves binding of the ubiquitin ligase Nedd4-2 to a proline-proline-serine-tyrosine sequence of Nav1.5, designated the PY-motif. We investigated the biophysical properties of the LQT3-associated SCN5A-p.Y1977N mutation located in the Nav1.5 PY-motif, both in HEK293 cells as well as in newly generated mice harboring the mouse homolog mutation Scn5a-p.Y1981N. We found that in HEK293 cells, the SCN5A-p.Y1977N mutation abolished the interaction between Nav1.5 and Nedd4-2, suppressed PY-motif-dependent ubiquitylation of Nav1.5, and consequently abrogated Nedd4-2 induced sodium current (INa) decrease. Nevertheless, homozygous mice harboring the Scn5a-p.Y1981N mutation showed no electrophysiological alterations nor changes in AP or (late) INa properties, questioning the in vivo relevance of the PY-motif. Our findings suggest the presence of compensatory mechanisms, with additional, as yet unknown, factors likely required to reduce the “ubiquitylation reserve” of Nav1.5. Future identification of such modulatory factors may identify potential triggers for arrhythmias and sudden cardiac death in the setting of LQT3 mutations.
Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies
Authors: Soares Ricardo O. S. , Losada Daniele M. , Jordani Maria C. , Évora Paulo , Castro-e-Silva Orlando
Published: October 2019

Ischemia/reperfusion injury (IRI) permeates a variety of diseases and is a ubiquitous concern in every transplantation proceeding, from whole organs to modest grafts. Given its significance, efforts to evade the damaging effects of both ischemia and reperfusion are abundant in the literature and they consist of several strategies, such as applying pre-ischemic conditioning protocols, improving protection from preservation solutions, thus providing extended cold ischemia time and so on. In this review, we describe many of the latest pharmacological approaches that have been proven effective against IRI, while also revisiting well-established concepts and presenting recent pathophysiological findings in this ever-expanding field. A plethora of promising protocols has emerged in the last few years. They have been showing exciting results regarding protection against IRI by employing drugs that engage several strategies, such as modulating cell-surviving pathways, evading oxidative damage, physically protecting cell membrane integrity, and enhancing cell energetics.
Integration of Transcriptomics and Metabolomics for Pepper (Capsicum annuum L.) in Response to Heat Stress
Authors: Wang Jing , Lv Junheng , Liu Zhoubin , Liu Yuhua , Song Jingshuang , Ma Yanqing , Ou Lijun , Zhang Xilu , Liang Chengliang , Wang Fei , Juntawong Niran , Jiao Chunhai , Chen Wenchao , Zou Xuexiao
Published: October 2019

Heat stress (HS), caused by extremely high temperatures, is one of the most severe forms of abiotic stress in pepper. In the present study, we studied the transcriptome and metabolome of a heat-tolerant cultivar (17CL30) and a heat-sensitive cultivar (05S180) under HS. Briefly, we identified 5754 and 5756 differentially expressed genes (DEGs) in 17CL30 and 05S180, respectively. Moreover, we also identified 94 and 108 differentially accumulated metabolites (DAMs) in 17CL30 and 05S180, respectively. Interestingly, there were many common HS-responsive genes (approximately 30%) in both pepper cultivars, despite the expression patterns of these HS-responsive genes being different in both cultivars. Notably, the expression changes of the most common HS-responsive genes were typically much more significant in 17CL30, which might explain why 17CL30 was more heat tolerant. Similar results were also obtained from metabolome data, especially amino acids, organic acids, flavonoids, and sugars. The changes in numerous genes and metabolites emphasized the complex response mechanisms involved in HS in pepper. Collectively, our study suggested that the glutathione metabolic pathway played a critical role in pepper response to HS and the higher accumulation ability of related genes and metabolites might be one of the primary reasons contributing to the heat resistance.
Obtaining Genome Sequences of Mutualistic Bacteria in Single Microcystis Colonies
Authors: Tu Jing , Chen Liang , Gao Shen , Zhang Junyi , Bi Changwei , Tao Yuhan , Lu Na , Lu Zuhong
Published: October 2019

Cells of Microcystis are associated with heterotrophic bacteria and organized in colonies in natural environment, which are basic elements in the mass occurrence of cyanobacterial species. Analyzing these colonies by using metagenomics is helpful to understand species composition and relationship. Meanwhile, the difference in population abundance among Microcystis colonies could be used to recover genome bins from metagenome assemblies. Herein, we designed a pipeline to obtain high-quality genomes of mutualistic bacteria from single natural Microcystis colonies. Single colonies were lysed, and then amplified by using multiple displacement amplification to overcome the DNA quantity limit. A two-step assembly was performed after sequencing and scaffolds were grouped into putative bins based on their differential-coverage among species. We analyzed six natural colonies of three prevailing Microcystis species from Lake Taihu. Clustering results proved that colonies of the same species were similar in the microbial community composition. Eight putative population genome bins with wide bacterial diversity and different GC content were identified based on coverage difference among colonies. At the phylum level, proteobacteria was the most abundant besides cyanobacteria. Six of the population bins were further refined into nearly complete genomes (completeness > 90%).
Sub-Lethal Doses of Clothianidin Inhibit the Conditioning and Biosensory Abilities of the Western Honeybee Apis mellifera
Authors: Bartling Merle T. , Vilcinskas Andreas , Lee Kwang-Zin
Published: October 2019

Insects play an important role in the stability of ecosystems by fulfilling key functions such as pollination and nutrient cycling, as well as acting as prey for amphibians, reptiles, birds and mammals. The global decline of insects is therefore a cause for concern, and the role of chemical pesticides must be examined carefully. The lethal effects of insecticides are well understood, but sub-lethal concentrations have not been studied in sufficient detail. We therefore used the western honeybee Apis mellifera as a model to test the effect of the neonicotinoid insecticide clothianidin on the movement, biosensory abilities and odor-dependent conditioning of insects, titrating from lethal to sub-lethal doses. Bees treated with sub-lethal doses showed no significant movement impairment compared to untreated control bees, but their ability to react to an aversive stimulus was inhibited. These results show that clothianidin is not only highly toxic to honeybees, but can, at lower doses, also disrupt the biosensory capabilities of survivors, probably reducing fitness at the individual level. In our study, sub-lethal doses of clothianidin altered the biosensory abilities of the honeybee; possible consequences at the colony level are discussed.
Comparison of Placental Three-Dimensional Power Doppler Vascular Indices and Placental Volume in Pregnancies with Small for Gestational Age Neonates
Authors: Chen Sue-Jar , Chen Chie-Pein , Sun Fang-Ju , Chen Chen-Yu
Published: October 2019

This prospective observational study aimed to compare the changes in placental vascular indices and placental volume using three-dimensional power Doppler (3DPD) ultrasound in pregnancies with small for gestational age (SGA) neonates. We enrolled 396 women with singleton pregnancies from September 2013 to June 2016. Placental vascular indices, including the vascularization index (VI), flow index (FI), and vascularization flow index (VFI), and placental volume were obtained using 3DPD ultrasound in the first and second trimesters. Of the enrolled women, 21 delivered SGA neonates and 375 did not. In the first trimester, the SGA group had a significantly lower mean FI (25.10 ± 7.51 versus 33.10 ± 10.97, p < 0.001) and VFI (4.59 ± 1.95 versus 6.28 ± 2.35, p = 0.001) than the non-SGA group. However, there was no significant difference in the placental volume between the two groups during the first trimester. In the second trimester, the SGA group also had a significantly lower mean FI (27.08 ± 7.97 versus 31.54 ± 11.01, p = 0.022) and VFI (6.68 ± 1.71 versus 8.68 ± 3.09, p < 0.001) than the non-SGA group. In addition, a significantly smaller placental volume was noted in the SGA group (104.80 ± 24.23 cm3 versus 122.67 ± 26.35 cm3, p = 0.003) than in the non-SGA group during the second trimester. The results showed that a decreased placental VFI occurred earlier than a decreased placental volume in SGA pregnancies.
18F–Choline PET/CT Identifies High-Grade Prostate Cancer Lesions Expressing Bone Biomarkers
Authors: Urbano Nicoletta , Scimeca Manuel , Crocco Antonio , Mauriello Alessandro , Bonanno Elena , Schillaci Orazio
Published: October 2019

The main aim of this study was to investigate the possible association between 18F–choline uptake and histopathological features of prostate biopsies such as the Gleason Group and the expression of both epithelial to mesenchymal transition (vimentin) and bone mineralization (bone morphogenetics protein (BMP)-2, runt-related transcription factor 2 (RUNX2), receptor activator of nuclear factor-κB ligand (RANKL), vitamin D receptor (VDR), and pentraxin 3 (PTX3) in situ biomarkers. To this end, we enrolled 79 consecutive prostate cancer patients that underwent both the 18F–choline PET/CT analysis and the prostate bioptic procedure. The standardized uptake value (SUV) average values were collected from 18F–choline PET/CT analysis whereas Gleason Group and immunostaining data were collected from paraffin-embedded sections. Histological classification showed a heterogenous population including both low/intermediate and high-grade prostate cancers. A significant increase of 18F–choline uptake in high-grade prostate lesions (Gleason Score ≥8) was found. Also, linear regression analysis showed a significant correlation between 18F–choline uptake and the number of vimentin, RANKL, VDR, or PTX3 positive prostate cancer cells. Conversely, we observed no significant association between 18F–choline uptake and the expression of bone biomarkers involved in the early phases of osteoblast differentiation (BMP-2, RUNX2). In conclusion, results here reported can lay the foundation for the use of 18F–choline positron emission tomography (PET)/computed tomography (CT) as a diagnostic tool capable of identifying high-grade prostate cancer lesions expressing bone biomarkers.
Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma
Authors: Bottani Michela , Banfi Giuseppe , Lombardi Giovanni
Published: October 2019

An early cancer diagnosis is essential to treat and manage patients, but it is difficult to achieve this goal due to the still too low specificity and sensitivity of classical methods (imaging, actual biomarkers), together with the high invasiveness of tissue biopsies. The discovery of novel, reliable, and easily collectable cancer markers is a topic of interest, with human biofluids, especially blood, as important sources of minimal invasive biomarkers such as circulating microRNAs (miRNAs), the most promising. MiRNAs are small non-coding RNAs and known epigenetic modulators of gene expression, with specific roles in cancer development/progression, which are next to be implemented in the clinical routine as biomarkers for early diagnosis and the efficient monitoring of tumor progression and treatment response. Unfortunately, several issues regarding their validation process are still to be resolved. In this review, updated findings specifically focused on the clinical relevance of circulating miRNAs as prognostic and diagnostic biomarkers for the most prevalent cancer types (breast, lung, and prostate cancers in adults, and osteosarcoma in children) are described. In addition, deep analysis of pre-analytical, analytical, and post-analytical issues still affecting the circulation of miRNAs’ validation process and routine implementation is included.
Electrophoretic Deposition of WS2 Flakes on Nanoholes Arrays—Role of Used Suspension Medium
Authors: Mosconi Dario , Giovannini Giorgia , Maccaferri Nicolò , Serri Michele , Agnoli Stefano , Garoli Denis
Published: October 2019

Here we optimized the electrophoretic deposition process for the fabrication of WS2 plasmonic nanohole integrated structures. We showed how the conditions used for site-selective deposition influenced the properties of the deposited flakes. In particular, we investigated the effect of different suspension buffers used during the deposition both in the efficiency of the process and in the stability of WS2 flakes, which were deposited on an ordered arrays of plasmonic nanostructures. We observed that a proper buffer can significantly facilitate the deposition process, keeping the material stable with respect to oxidation and contamination. Moreover, the integrated plasmonic structures that can be prepared with this process can be applied to enhanced spectroscopies and for the preparation of 2D nanopores.
A Comparative Study on Color Stability of Anthocyanin Hybrid Pigments Derived from 1D and 2D Clay Minerals
Authors: Li Shue , Mu Bin , Wang Xiaowen , Kang Yuru , Wang Aiqin
Published: October 2019

Anthocyanin extracted from the fresh blue berry fruits was loaded onto different clay minerals including one-dimensional tubular halloysite and fibrous sepiolite, and two-dimensional lamellar kaolinite and montmorillonite to fabricate reversible allochroic hybrid pigments. The effect of the possible interaction mechanism between anthocyanin and clay minerals on the color stability of hybrid pigments was investigated. Due to the difference in the structures and properties of clay minerals, natural anthocyanin was inclined to be absorbed on the surface and intercalated into the interlayer of 2:1 type layered montmorillonite, while it was mainly anchored on the surface of 1:1 type kaolinite and halloysite. By contrast, it was simultaneously loaded on the surface and confined into the nanochannels and/or grooves of 2:1 type chain-layered sepiolite. Interestingly, the resulting hybrid pigments presented good thermal stability and resistance to chemical reagents, as well as reversible gas-sensitive allochroic behavior in HCl or NH3 gases, especially anthocyanin/sepiolite hybrid pigments due to the shielding effect of the well-defined nanochannels and grooves of sepiolite. Based on this color-change behavior, a simple pH test paper was also prepared with obvious color change at different pH values by coating the filter paper with anthocyanin/sepiolite hybrid pigments.
Microstructure and Mechanical Properties of Laser Welded Al-Si Coated Hot-Press-Forming Steel Joints
Authors: Chen Xi , Lei Zhenglong , Chen Yanbin , Jiang Meng , Tian Ze , Bi Jiang , Lin Sanbao
Published: October 2019

High strength steel has attracted a lot of attention due to its excellent advantage of weight reduction. A thin Al-Si coating covered on the surface of hot-press-forming (HPF) steel offers functions of antioxidation and decarburization under high temperature processing conditions. In this study, the microstructure characteristic, phase, microhardness, and tensile strength of laser welded Al-Si coated HPF steel joints were investigated at different laser powers. Experimental results show that the welding process becomes unstable because of metallic vapor generated by ablation of the coating. Some of the white bright rippled Fe-Al phase was observed to be distributed in the fusion zone randomly. It is found that microhardness, tensile strength, and cupping test qualification rate decreases with the increase of the laser power. For the 1.1 kW laser power, the sound weld performs the best mechanical properties: Microhardness of 466.53 HV and tensile strength of 1349.9 MPa.
Naturally Drug-Loaded Chitin: Isolation and Applications
Authors: Kovalchuk Valentine , Voronkina Alona , Binnewerg Björn , Schubert Mario , Muzychka Liubov , Wysokowski Marcin , Tsurkan Mikhail V. , Bechmann Nicole , Petrenko Iaroslav , Fursov Andriy , Martinovic Rajko , Ivanenko Viatcheslav N. , Fromont Jane , Smolii Oleg B. , Joseph Yvonne , Giovine Marco , Erpenbeck Dirk , Gelinsky Michael , Springer Armin , Guan Kaomei , Bornstein Stefan R. , Ehrlich Hermann
Published: October 2019

Naturally occurring three-dimensional (3D) biopolymer-based matrices that can be used in different biomedical applications are sustainable alternatives to various artificial 3D materials. For this purpose, chitin-based structures from marine sponges are very promising substitutes. Marine sponges from the order Verongiida (class Demospongiae) are typical examples of demosponges with well-developed chitinous skeletons. In particular, species belonging to the family Ianthellidae possess chitinous, flat, fan-like fibrous skeletons with a unique, microporous 3D architecture that makes them particularly interesting for applications. In this work, we focus our attention on the demosponge Ianthella flabelliformis (Linnaeus, 1759) for simultaneous extraction of both naturally occurring (“ready-to-use”) chitin scaffolds, and biologically active bromotyrosines which are recognized as potential antibiotic, antitumor, and marine antifouling substances. We show that selected bromotyrosines are located within pigmental cells which, however, are localized within chitinous skeletal fibers of I. flabelliformis. A two-step reaction provides two products: treatment with methanol extracts the bromotyrosine compounds bastadin 25 and araplysillin-I N20 sulfamate, and a subsequent treatment with acetic acid and sodium hydroxide exposes the 3D chitinous scaffold. This scaffold is a mesh-like structure, which retains its capillary network, and its use as a potential drug delivery biomaterial was examined for the first time. The results demonstrate that sponge-derived chitin scaffolds, impregnated with decamethoxine, effectively inhibit growth of the human pathogen Staphylococcus aureus in an agar diffusion assay.
Study of the Tool Wear Process in the Dry Turning of Al–Cu Alloy
Authors: Batista Moises , Del Sol Irene , Gomez-Parra Alvaro , Ramirez-Peña Magdalena , Salguero Jorge
Published: October 2019

Light alloy machining is a widely implemented process that is usually used in the presence of cutting fluids to reduce wear and increase tool life. The use of coolants during machining presents negative environmental impacts, which has increased interest in reducing and even eliminating their use. In order to obtain ecofriendly machining processes, it will be necessary to suppress the use of cutting fluids, in a trend called “dry machining”. This fact forces machines to work under aggressive cutting conditions, producing adhesion wear that affects the integrity of the parts’ surfaces. This study describes cutting tool wear mechanisms in machining of UNS A92024 samples under dry cutting conditions. Energy dispersive spectroscopy (EDS) analysis shows the different compositions of the adhered layers. Roughness is also positively affected by the change of the cutting geometry produced in the tool.
Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
Authors: Bird Matthew J , Adant Isabelle , Windmolders Petra , Vander Elst Ingrid , Felgueira Catarina , Altassan Ruqaiah , Gruenert Sarah C , Ghesquière Bart , Witters Peter , Cassiman David , Vermeersch Pieter
Published: October 2019

Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of the mitochondrial oxidative phosphorylation (OXPHOS) complexes remains the gold standard, oxygraphy could offer several advantages. To this end, we compared the diagnostic performance of both techniques in a cohort of 34 genetically defined PMD patient fibroblast cell lines. We observed that oxygraphy slightly outperformed enzymology for sensitivity (79 ± 17% versus 68 ± 15%, mean and 95% CI), and had a better discriminatory power, identifying 58 ± 17% versus 35 ± 17% as “very likely” for oxygraphy and enzymology, respectively. The techniques did, however, offer synergistic diagnostic prediction, as the sensitivity rose to 88 ± 11% when considered together. Similarly, the techniques offered varying defect specific information, such as the ability of enzymology to identify isolated OXPHOS deficiencies, while oxygraphy pinpointed PDHC mutations and captured POLG mutations that were otherwise missed by enzymology. In summary, oxygraphy provides useful information for the diagnosis of PMD, and should be considered in conjunction with enzymology for the diagnosis of PMD.
Petrographical and Geochemical Signatures Linked to Fe/Mn Reduction in Subsurface Marine Sediments from the Hydrate-Bearing Area, Dongsha, the South China Sea
Authors: Xiao Xi , Zhou Qian-Zhi , Fu Shao-Ying , Liang Qian-Yong , Xu Xiang-Po , Li Yan , Wang Jiang-Hai
Published: October 2019

Fe and Mn oxides and (oxy)-hydroxides are the most abundant solid-phase electron acceptors in marine sediments, and dissimilatory Fe/Mn reduction usually links with the anaerobic oxidation of methane (AOM) and organic matter oxidation (OMO) in sediments. In this study, we report the results from subsurface marine sediments in the Dongsha hydrate-bearing area in the South China Sea. The petrological and geochemical signatures show that the Fe/Mn reduction mediated by AOM and OMO might occur in sediments above the sulfate-methane transition zone. X-ray diffraction and scanning electron microscopy analyses of sediments indicate that Fe(III)/Mn(IV)-oxides and authigenic carbonate minerals coexisted in the Fe/Mn reduction zone. The lower δ13C values of dissolved inorganic carbon, coupled with an evident increase in total inorganic carbon contents and a decrease in Ca2+ and Mg2+ concentrations indicate the onset of AOM in this zone, and the greater variation of PO43− and NH4+ concentrations in pore water suggests the higher OMO rates in subsurface sediments. Geochemical and mineralogical analyses suggest that the previously buried Fe(III)/Mn(IV) oxides might be activated and lead to the onset of Fe/Mn reduction induced by AOM and OMO. These findings may extend our understanding of the biogeochemical processes involved in Fe/Mn reduction in continental shelves with abundant methane, organic matter, and terrigenous metal oxides.
Cesium Sorption and Desorption on Glauconite, Bentonite, Zeolite, and Diatomite
Authors: Belousov Petr , Semenkova Anna , Egorova Tolganay , Romanchuk Anna , Zakusin Sergey , Dorzhieva Olga , Tyupina Ekaterina , Izosimova Yulia , Tolpeshta Inna , Chernov Michail , Krupskaya Victoria
Published: October 2019

This study is devoted to studying the sorption of 137Cs on mineral sorbents at a wide pH range, from 2 to 10, as well as to studying sorption mechanisms. In order to obtain the most reliable sorption characteristics, samples of high purity were examined as sorbents: bentonite, glauconite, zeolite, and diatomite. A detailed description of their mineral composition, cation exchange capacity and specific surface of sorbents is given. XRD, XRF, FTIR, SEM, and BET adsorption methods were used for assaying. The sorption and desorption values were identified for each sorbent. As a result of the conducted research, it can be concluded that 137Cs sorption mainly occurs through the exchange reaction on zeolite, glauconite and bentonite. The highest cesium Kd was observed on zeolite due to its high CEC and amounted to 4.05 mg/L at pH 7. The higher sorption capacity of glauconite in comparison with bentonite is primarily due to the high layer charge which is mainly localized in tetrahedral sheets, and to the existence of highly selective sorption sites (frayed edge sites) on the glauconite surface. Diatomite showed the lowest sorption capacity provided by the presence of a small quantity of smectite and kaolinite in its composition. The values of desorption increase in the following order: zeolite < bentonite ~ diatomite < glauconite.
Potential for Mineral Carbonation of CO2 in Pleistocene Basaltic Rocks in Volos Region (Central Greece)
Authors: Koukouzas Nikolaos , Koutsovitis Petros , Tyrologou Pavlos , Karkalis Christos , Arvanitis Apostolos
Published: October 2019

Pleistocene alkaline basaltic lavas crop out in the region of Volos at the localities of Microthives and Porphyrio. Results from detailed petrographic study show porphyritic textures with varying porosity between 15% and 23%. Data from deep and shallow water samples were analysed and belong to the Ca-Mg-Na-HCO3-Cl and the Ca-Mg-HCO3 hydrochemical types. Irrigation wells have provided groundwater temperatures reaching up to ~30 °C. Water samples obtained from depths ranging between 170 and 250 m. The enhanced temperature of the groundwater is provided by a recent-inactive magmatic heating source. Comparable temperatures are also recorded in adjacent regions in which basalts of similar composition and age crop out. Estimations based on our findings indicate that basaltic rocks from the region of Volos have the appropriate physicochemical properties for the implementation of a financially feasible CO2 capture and storage scenario. Their silica-undersaturated alkaline composition, the abundance of Ca-bearing minerals, low alteration grade, and high porosity provide significant advantages for CO2 mineral carbonation. Preliminary calculations suggest that potential pilot projects at the Microthives and Porphyrio basaltic formations can store 64,800 and 21,600 tons of CO2, respectively.
Synthesis of Novel Baicalein Amino Acid Derivatives and Biological Evaluation as Neuroprotective Agents
Authors: Jia Xiaohui , Jia Menglu , Yang Yuqin , Wang Di , Zhou Fei , Zhang Wenxi , Huang Xuemei , Guo Wenbo , Cai Desheng , Chen Hongshan , Qi Jinchai , Zhou Shuqi , Ren Haomiao , Xu Bing , Ma Tao , Wang Penglong , Lei Haimin
Published: October 2019

Baicalein, a famously effective component of the traditional Chinese medicine Rhizoma Huang Qin (Scutellaria altissima L.), has been proved to have potent neuroprotection and anti-platelet aggregation effects with few side effects. Meanwhile, recent studies have revealed that the introduction of amino acid to baicalein could improve its neuroprotective activity. In the present study, a series of novel baicalein amino acid derivatives were designed, synthesized, and screened for their neuroprotective effect against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells and toxicity on the normal H9C2 cell line by standard methylthiazol tetrazolium (MTT) assay. In addition, all of the newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and high resolution mass spectrometry (HR-MS). The results showed that most of the compounds provided more potent neuroprotection than baicalein, and were equivalent to the positive drug edaravin. They showed no obvious cytotoxicity on normal H9C2 cells. Notably, the most active compound 8 displayed the highest protective effect (50% effective concentration (EC50) = 4.31 μM) against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells, which was much better than the baicalein (EC50 = 24.77 μM) and edaravin (EC50 = 5.62 μM). Further research on the chick chorioallantoic membrane (CAM) model indicated that compound 8 could significantly increase angiogenesis, which might promote neurovascular proliferation. The detection of apoptosis analysis showed that compound 8 could dramatically alleviate morphological manifestations of cell damage. Moreover, the benzyloxycarbonyl (cbz)-protected baicalein amino acid derivatives showed better neuroprotective activity than the t-Butyloxy carbonyl (boc)-protected derivatives.
20(S)-Ginsenoside Rg3 Promotes HeLa Cell Apoptosis by Regulating Autophagy
Authors: Bian Shuai , Zhao Yue , Li Fangyu , Lu Shuyan , Wang Siming , Bai Xueyuan , Liu Meichen , Zhao Daqing , Wang Jiawen , Guo Dean
Published: October 2019

20(S)-Ginsenoside Rg3 (GRg3) has various bioactivities including anti-cancer effects and inhibition of autophagy. However, no reports have investigated the appearance of autophagy or the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRg3. Cell viability was measured by CCK-8 (cell counting kit-8) assays. Apoptosis and the cell cycle were analyzed by Hoechst 33342 staining and flow cytometry. Apoptotic pathways were examined by ROS (reactive oxygen species) determination and rhodamine 123 assays. Western blot analysis was used to determine changes in protein levels. Autophagy induction was monitored by acidic vesicular organelle staining and EGFP-LC3 transfection. 20(S)-GRg3 inhibited autophagy of cells in a starved state, making it impossible for cells to maintain a steady state through autophagy, and then induced apoptosis. 20(S)-GRg3 blocked the late stage of autophagy (fusion of lysosomes and degradation of autophagic lysosomes), including a decrease in acidic vesicular organelle fluorescence, increased LC3 I–II conversion, accumulation of EGFP-LC3 fluorescence, GFP-mRFP-LC3 red-green fluorescence ratio, degradation of the substrate p62, and loss of the balance between autophagy and apoptosis, which induced apoptosis. ROS increased, the mitochondrial membrane potential decreased, apoptotic inducer AIF was released from mitochondria, and nuclear transfer occurred, triggering a series of subsequent apoptotic events. Autophagy inducer rapamycin inhibited the apoptosis induced by 20(S)-GRg3, whereas autophagy inhibitor BA1 promoted apoptosis induced by 20(S)-GRg3. Therefore, 20(S)-GRg3 promoted HeLa cell apoptosis by regulating autophagy. In the autophagic state, 20(S)-GRg3 can be used as a novel autophagy inhibitor in synergy with tumor-blocking therapies such as chemotherapy, which supports its application in the medical field.
Raman Spectroscopy for the Competition of Hydrogen Bonds in Ternary (H2O–THF–DMSO) Aqueous Solutions
Authors: Liu Shiliang , Zhang Mingzhe , Huang Baokun , Wu Nannan , Ouyang Shunli
Published: October 2019

The effects of hydrogen bonds on the molecular structure of water-tetrahydrofuran (H2O–THF), water-dimethyl sulfoxide (H2O–DMSO), and water-tetrahydrofuran-dimethyl sulfoxide (H2O–THF–DMSO) in binary aqueous solutions and ternary aqueous solutions were studied using Raman spectroscopy. The results indicate that in the binary aqueous solution, the addition of THF and DMSO will generate hydrogen bonds with water molecules, resulting in changes in the peak positions of S=O bonds and C–O bonds. Compared with the binary aqueous solutions, the hydrogen bonds between DMSO and THF, and the hydrogen bonds between DMSO and H2O in the ternary aqueous solutions are competitive, and the hydrogen bond competition is susceptible to water content. In addition, the formation of hydrogen bonds will destroy the fully hydrogen-bonded water and make it change to the partially hydrogen-bonded water. By fitting the spectra into the three Gaussian components assigned to water molecules with different hydrogen bonding (HB) environments, these spectral features are interpreted by a mechanism that H2O in different solution systems has equal types of water molecules with similar HB degrees-fully hydrogen-bonded H2O (FHW) and partially hydrogen-bonded H2O (PHW). The ratio of the intensity transition from FHW to PHW is determined based on Gaussian fitting. Therefore, the variation of hydrogen bond competition can be supplemented by the intensity ratio of PHW/FHW ((IC2 + IC3)/IC1). This study provides an experimental basis for enriching the hydrogen bonding theory of multivariate aqueous solution systems.
A Facile Method for Preparing UiO-66 Encapsulated Ru Catalyst and its Application in Plasma-Assisted CO2 Methanation
Authors: Xu Weiwei , Dong Mengyue , Di Lanbo , Zhang Xiuling
Published: October 2019

With increasing applications of metal-organic frameworks (MOFs) in the field of gas separation and catalysis, the preparation and performance research of encapsulating metal nanoparticles (NPs) into MOFs (M@MOF) have attracted extensive attention recently. Herein, an Ru@UiO-66 catalyst is prepared by a one-step method. Ru NPs are encapsulated in situ in the UiO-66 skeleton structure during the synthesis of UiO-66 metal-organic framework via a solvothermal method, and its catalytic activity for CO2 methanation with the synergy of cold plasma is studied. The crystallinity and structural integrity of UiO-66 is maintained after encapsulating Ru NPs according to the X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). As illustrated by X-ray photoelectron spectroscopy (XPS), high resolution transmission electron microscopy (HRTEM), and mapping analysis, the Ru species of the hydration ruthenium trichloride precursor are reduced to metallic Ru NPs without additional reducing processes during the synthesis of Ru@UiO-66, and the Ru NPs are uniformly distributed inside the Ru@UiO-66. Thermogravimetric analysis (TGA) and N2 sorption analysis show that the specific surface area and thermal stability of Ru@UiO-66 decrease slightly compared with that of UiO-66 and was ascribed to the encapsulation of Ru NPs in the UiO-66 skeleton. The results of plasma-assisted catalytic CO2 methanation indicate that Ru@UiO-66 exhibits excellent catalytic activity. CO2 conversion and CH4 selectivity over Ru@UiO-66 reached 72.2% and 95.4% under 13.0 W of discharge power and a 30 mL·min−1 gas flow rate ( V H 2 : V C O 2 = 4 : 1 ), respectively. Both values are significantly higher than pure UiO-66 with plasma and Ru/Al2O3 with plasma. The enhanced performance of Ru@UiO-66 is attributed to its unique framework structure and excellent dispersion of Ru NPs.
Ultra-High Refractive Index Sensing Structure Based on a Metal-Insulator-Metal Waveguide-Coupled T-Shape Cavity with Metal Nanorod Defects
Authors: Chou Chau Yuan-Fong , Chou Chao Chung-Ting , Huang Hung Ji , Kumara N. T. R. N. , Lim Chee Ming , Chiang Hai-Pang
Published: October 2019

An ultra-high plasmonic refractive index sensing structure composed of a metal–insulator–metal (MIM) waveguide coupled to a T-shape cavity and several metal nanorod defects is proposed and investigated by using finite element method. The designed plasmonic MIM waveguide can constitute a cavity resonance zone and the metal nanorod defects can effectively trap the light in the T-shape cavity. The results reveal that both the size of defects in wider rectangular cavity and the length of narrower rectangular cavity are primary factors increasing the sensitivity performance. The sensitivity can achieve as high as 8280 nm/RIU (RIU denotes the refractive index unit), which is the highest sensitivity reported in plasmonic MIM waveguide-based sensors to our knowledge. In addition, the proposed structure can also serve as a temperature sensor with temperature sensitivity as high as 3.30 nm/°C. The designed structure with simplicity and ease of fabrication can be applied in sensitivity nanometer scale refractive index sensor and may potentially be used in optical on-chip nanosensor.
Biomimetic Hydroxyapatite on Graphene Supports for Biomedical Applications: A Review
Authors: Wei Gang , Gong Coucong , Hu Keke , Wang Yabin , Zhang Yantu
Published: October 2019

Hydroxyapatite (HA) has been widely used in fields of materials science, tissue engineering, biomedicine, energy and environmental science, and analytical science due to its simple preparation, low-cost, and high biocompatibility. To overcome the weak mechanical properties of pure HA, various reinforcing materials were incorporated with HA to form high-performance composite materials. Due to the unique structural, biological, electrical, mechanical, thermal, and optical properties, graphene has exhibited great potentials for supporting the biomimetic synthesis of HA. In this review, we present recent advance in the biomimetic synthesis of HA on graphene supports for biomedical applications. More focuses on the biomimetic synthesis methods of HA and HA on graphene supports, as well as the biomedical applications of biomimetic graphene-HA nanohybrids in drug delivery, cell growth, bone regeneration, biosensors, and antibacterial test are performed. We believe that this review is state-of-the-art, and it will be valuable for readers to understand the biomimetic synthesis mechanisms of HA and other bioactive minerals, at the same time it can inspire the design and synthesis of graphene-based novel nanomaterials for advanced applications.
Spectral Modulation of Optofluidic Coupled-Microdisk Lasers in Aqueous Media
Authors: Guo Zhihe , Wang Haotian , Zhao Chenming , Chen Lin , Liu Sheng , Hu Jinliang , Zhou Yi , Wu Xiang
Published: October 2019

We present the spectral modulation of an optofluidic microdisk device and investigate the mechanism and characteristics of the microdisk laser in aqueous media. The optofluidic microdisk device combines a solid-state dye-doped polymer microdisk with a microfluidic channel device, whose optical field can interact with the aqueous media. Interesting phenomena, such as mode splitting and single-mode lasing in the laser spectrum, can be observed in two coupled microdisks under the pump laser. We modulated the spectra by changing the gap of the two coupled microdisks, the refractive indices of the aqueous media, and the position of a pump light, namely, selective pumping schemes. This optofluidic microlaser provides a method to modulate the laser spectra precisely and flexibly, which will help to further understand spectral properties of coupled microcavity laser systems and develop potential applications in photobiology and photomedicine.
A Rational Explanation of Limited FMD Vaccine Uptake in Endemic Regions
Authors: Railey Ashley F. , Marsh Thomas L.
Published: October 2019

Vaccination for foot-and-mouth (FMD) disease remains low in parts of Africa despite the existence of vaccines. In East Africa, the presence of multiple virus serotypes and sub-types makes matching a vaccine with the circulating virus type in the field, or providing a high potency vaccine, a challenge. In this paper we use game theory to show that the resulting vaccine uncertainty associated with these vaccination conditions in an endemic setting help explain the low vaccine uptake. We evaluate vaccination for FMD in the context of East Africa due to FMD being endemic in the region, the diversity of FMD virus types, and barriers to implementing other disease control measures, such as controlled movements. We incorporate these conditions into a vaccination game setting and compare the payoffs to those of a traditional vaccination game for seasonal influenza and commercial livestock vaccination in a developed country context. In showing that vaccination provides households with a lower payoff than not vaccinating, our simple game theoretical explanation supports existing evidence calling for improved vaccine quality and efforts to enhance surveillance to provide early information on disease status.
Effect of Polymer Permeability and Solvent Removal Rate on In Situ Forming Implants: Drug Burst Release and Microstructure
Authors: Zhang Xiaowei , Yang Liqun , Zhang Chong , Liu Danhua , Meng Shu , Zhang Wei , Meng Shengnan
Published: October 2019

To explore the mechanism of drug release and depot formation of in situ forming implants (ISFIs), osthole-loaded ISFIs were prepared by dissolving polylactide, poly(lactide-co-glycolide), polycaprolactone, or poly(trimethylene carbonate) in different organic solvents, including N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), and triacetin (TA). Drug release, polymer degradation, solvent removal rate and depot microstructure were examined. The burst release effect could be reduced by using solvents exhibit slow forming phase inversion and less permeable polymers. Both the drug burst release and polymer depot microstructure were closely related to the removal rate of organic solvent. Polymers with higher permeability often displayed faster drug and solvent diffusion rates. Due to high polymer-solvent affinity, some of the organic solvent remained in the depot even after the implant was completely formed. The residual of organic solvent could be predicted by solubility parameters. The ISFI showed a lower initial release in vivo than that in vitro. In summary, the effects of different polymers and solvents on drug release and depot formation in ISFI systems were extensively investigated and discussed in this article. The two main factors, polymer permeability and solvent removal rate, were involved in different stages of drug release and depot formation in ISFI systems.
Pharmaceutical Benefits of Fluticasone Propionate Association to Delivery Systems: In Vitro and In Vivo Evaluation
Authors: Dogbe Marina G. , Mafilaza Ambinintsoa Yattussia , Eleutério Carla Vânia , Cabral-Marques Helena , Simões Sandra , Gaspar Maria Manuela
Published: October 2019

The objective of the present work was to characterize the ability of liposomes and cyclodextrin (CyD) complexes to modulate the in vivo profile of fluticasone (FTZ). In vitro cell compatibility tests were performed, exposing A549 cells to FTZ in the free form and FTZ associated to liposomes and complexed with CyD. The in vivo fate of a selected FTZ liposomal formulation and of several FTZ CyD complexes was achieved following intranasal instillation or pulmonary administration in BALB/c mice, respectively. For pulmonary administration, an inhalation chamber was constructed to enable the simultaneously pulmonary administration to six mice. Thirty minutes and 3 h after administration, mice were sacrificed, their blood, lungs, livers, and spleens were removed, and FTZ level was determined by HPLC using an extraction procedure. The in vitro tests revealed no toxic effects of FTZ formulations, as cellular viability was always superior to 90% for FTZ concentrations ranging from 5 to 60 µM 72 h after incubation. The in vivo biodistribution results showed that FTZ incorporated in liposomes resulted in 20 and 30 times higher accumulation in the lungs in comparison with free FTZ, at 0.5 and 3 h after i.n. administration, respectively. FTZ associated to Hydroxypropyl-γ-cyclodextrin (HP-CyD) was the complex that permitted the higher accumulation of FTZ in the lungs in comparison with the respective free form. The results also suggest that the inhalation chamber apparatus can effectively facilitate the evaluation of in vivo inhalation. The establishment of an animal model of asthma allows us to further study the therapeutic efficacy of the developed FTZ formulations.
The Plant NF-Y DNA Matrix In Vitro and In Vivo
Authors: Gnesutta Nerina , Chiara Matteo , Bernardini Andrea , Balestra Matteo , Horner David S. , Mantovani Roberto
Published: October 2019

Nuclear Factor Y (NF-Y) is an evolutionarily conserved trimer formed by a Histone-Fold Domain (HFD) heterodimeric module shared by core histones, and the sequence-specific NF-YA subunit. In plants, the genes encoding each of the three subunits have expanded in number, giving rise to hundreds of potential trimers. While in mammals NF-Y binds a well-characterized motif, with a defined matrix centered on the CCAAT box, the specificity of the plant trimers has yet to be determined. Here we report that Arabidopsis thaliana NF-Y trimeric complexes, containing two different NF-YA subunits, bind DNA in vitro with similar affinities. We assayed precisely sequence-specificity by saturation mutagenesis, and analyzed genomic DNA sites bound in vivo by selected HFDs. The plant NF-Y CCAAT matrix is different in nucleotides flanking CCAAT with respect to the mammalian matrix, in vitro and in vivo. Our data point to flexible DNA-binding rules by plant NF-Ys, serving the scope of adapting to a diverse audience of genomic motifs.
Mesoscopic Detection of the Influence of a Third Component on the Self-Assembly Structure of A2B Star Copolymer in Thin Films
Authors: Mu Dan , Li Jian-Quan , Cong Xing-Shun , Zhang Han
Published: October 2019

The most common self-assembly structure for A2B copolymer is the micellar structure with B/A segments being the core/corona, which greatly limits its application range. Following the principle of structure deciding the properties, a reformation in the molecular structure of A2B copolymer is made by appending three segments of a third component C with the same length to the three arms, resulting (AC)2CB 3-miktoarm star terpolymer. A reverse micellar structure in self-assembly is expected by regulating the C length and the pairwise repulsive strength of C to A/B, aiming to enrich its application range. Keeping both A and B lengths unchanged, when the repulsion strength of C to A is much stronger than C to B, from the results of mesoscopic simulations we found, with a progressive increase in C length, (AC)2CB terpolymer undergoes a transition in self-assembled structures, from a cylindrical structure with B component as the core, then to a deformed lamellar structure, and finally to a cylindrical structure with A component as the core. This reverse micellar structure is formed with the assistance of appended C segments, whose length is longer than half of B length, enhancing the flexibility of three arms, and further facilitating the aggregation of A component into the core. These results prove that the addition of a third component is a rational molecular design, in conjunction with some relevant parameters, enables the manufacturing of the desired self-assembly structure while avoiding excessive changes in the involved factors.
Studying the Ring-Opening Polymerization of 1,5-Dioxepan-2-one with Organocatalysts
Authors: Xu Jinbao , Chen Yang , Xiao Wenhao , Zhang Jie , Bu Minglu , Zhang Xiaoqing , Lei Caihong
Published: October 2019

Three different organocatalysts, namely, 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris (dimethylamino) phosphoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene) (t-BuP4), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), have been used as 1,5-dioxepan-2-one (DXO) ring-opening polymerization (ROP) catalysts at varied reaction conditions. 1H NMR spectra, size exclusion chromatography (SEC) characterizations, and kinetic studies prove that the (co)polymerizations are proceeded in a controlled manner with the three organocatalysts. It is deduced that t-BuP4 and DBU catalysts are in an initiator/chain end activated ROP mechanism and TBD is in a nucleophilic ROP mechanism.