bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney
Authors: Khokhlova Tatiana D. , Schade George R. , Wang Yak-Nam , Buravkov Sergey V. , Chernikov Valeriy P. , Simon Julianna C. , Starr Frank , Maxwell Adam D. , Bailey Michael R. , Kreider Wayne , Khokhlova Vera A.
Published: December 2019

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5–30 pulses of 1–10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9–3.8 kW, sonication foci spaced 1–1.5 mm apart in a rectangular grid with 5–15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver.
Determining the Efficacy of a Hybridizing Agent in Wheat (Triticum aestivum L.)
Authors: Easterly Amanda C. , Stroup Walter W. , Garst Nicholas , Belamkar Vikas , Sarazin Jean-Benoit , Moittié Thierry , Ibrahim Amir M. H. , Rudd Jackie C. , Souza Edward , Baenziger P. Stephen
Published: December 2019

Hybrid wheat (Triticumspp.) has the potential to boost yields and enhance production under changing climates to feed the growing global population. Production of hybrid wheat seed relies on male sterility, the blocking of pollen production, to prevent self-pollination. One method of preventing self-pollination in the female plants is to apply a chemical hybridizing agent (CHA). However, some combinations of CHA and genotypes have lower levels of sterility, resulting in decreased hybrid purity. Differences in CHA efficacy are a challenge in producing hybrid wheat lines for commercial and experimental use. Our primary research questions were to estimate the levels of sterility for wheat genotypes treated with a CHA and determine the best way to analyze differences. We applied the CHA sintofen (1-(4-chlorphyl)-1,4-dihydro-5-(2-methoxyethoxy)-4-oxocinnoline-3-carboxylic acid; Croisor 100) to 27 genotypes in replicate. After spraying, we counted seed in bagged female heads to evaluate CHA efficacy and CHA-by-genotype interaction. Using logit and probit models with a threshold of 7 seeds, we found differences among genotypes in 2015. Sterility was higher in 2016 and fewer genotypic differences were found. When CHA-induced sterilization is less uniform as in 2015, zero-inflated and hurdle count models were superior to standard mixed models. These models calculate mean seed number and fit data with limit-bounded scales collected by agronomists and plant breeders to compare genotypic differences. These analyses can assist in selecting parents and identifying where additional optimization of CHA application needs to occur. There is little work in the literature examining the relationship between CHAs and genotypes, making this work fundamental to the future of hybrid wheat breeding.
Low vector competence in sylvatic mosquitoes limits Zika virus to initiate an enzootic cycle in South America
Authors: Fernandes Rosilainy S. , Bersot Maria I. , Castro Marcia G. , Telleria Erich Loza , Ferreira-de-Brito Anielly , Raphael Lidiane M. , Bonaldo Myrna C. , Lourenço-de-Oliveira Ricardo
Published: December 2019

Zika virus (ZIKV) has spread in the Americas since 2015 and the potential establishment of a sylvatic transmission cycle in the continent has been hypothesized. We evaluated vector competence of five sylvatic Neotropical mosquito species to two ZIKV isolates. Distinct batches of Haemagogus leucoceleanus, Sabethes albiprivus, Sabethes identicus, Aedes terrens and Aedes scapularis females were respectively orally challenged and inoculated intrathoracically with ZIKV. Orally challenged mosquitoes were refractory or exhibited low infection rates. Viral dissemination was detected only in Hg. leucocelaenus, but with very low rates. Virus was not detected in saliva of any mosquito orally challenged with ZIKV, regardless of viral isolate and incubation time. When intrathoracically injected, ZIKV disseminated in high rates in Hg. leucocelaenus, Sa. identicus and Sa. albpiprivus, but low transmission was detected in these species; very low dissemination and no transmission was detected in Ae. terrens and Ae. scapularis. Together these results suggest that genetically determined tissue barriers, especially in the midgut, play a vital role in inhibiting ZIKV for transmission in the tested sylvatic mosquito species. Thus, an independent enzootic transmission cycle for ZIKV in South America is very unlikely.
Neferine induces autophagy-dependent cell death in apoptosis-resistant cancers via ryanodine receptor and Ca2+-dependent mechanism
Authors: Law Betty Yuen Kwan , Michelangeli Francesco , Qu Yuan Qing , Xu Su-Wei , Han Yu , Mok Simon Wing Fai , Dias Ivo Ricardo de Seabra Rodrigues , Javed Masood-ul-Hassan , Chan Wai-Kit , Xue Wei-Wei , Yao Xiao-Jun , Zeng Wu , Zhang Hui , Wang Jing-Rong , Liu Liang , Wong Vincent Kam Wai
Published: December 2019

Resistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in cancer therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, the identification of medicinal compounds against chemoresistant cancer cells via new mechanism of action is highly desired. Autophagy is important in inducing cell death or survival in cancer therapy. Recently, novel autophagy activators isolated from natural products were shown to induce autophagic cell death in apoptosis-resistant cancer cells in a calcium-dependent manner. Therefore, enhancement of autophagy may serve as additional therapeutic strategy against these resistant cancers. By computational docking analysis, biochemical assays, and advanced live-cell imaging, we identified that neferine, a natural alkaloid from Nelumbo nucifera, induces autophagy by activating the ryanodine receptor and calcium release. With well-known apoptotic agents, such as staurosporine, taxol, doxorubicin, cisplatin and etoposide, utilized as controls, neferine was shown to induce autophagic cell death in a panel of cancer cells, including apoptosis-defective and -resistant cancer cells or isogenic cancer cells, via calcium mobilization through the activation of ryanodine receptor and Ulk-1-PERK and AMPK-mTOR signaling cascades. Taken together, this study provides insights into the cytotoxic mechanism of neferine-induced autophagy through ryanodine receptor activation in resistant cancers.
Dynamics of clusterin protein expression in the brain and plasma following experimental traumatic brain injury
Authors: Das Gupta Shalini , Lipponen Anssi , Paldanius Kaisa M. A. , Puhakka Noora , Pitkänen Asla
Published: December 2019

Progress in the preclinical and clinical development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI) necessitates the discovery of prognostic biomarkers for post-injury outcome. Our previous mRNA-seq data revealed a 1.8–2.5 fold increase in clusterin mRNA expression in lesioned brain areas in rats with lateral fluid-percussion injury (FPI)-induced TBI. On this basis, we hypothesized that TBI leads to increases in the brain levels of clusterin protein, and consequently, increased plasma clusterin levels. For evaluation, we induced TBI in adult male Sprague-Dawley rats (n = 80) by lateral FPI. We validated our mRNA-seq findings with RT-qPCR, confirming increased clusterin mRNA levels in the perilesional cortex (FC 3.3, p < 0.01) and ipsilateral thalamus (FC 2.4, p < 0.05) at 3 months post-TBI. Immunohistochemistry revealed a marked increase in extracellular clusterin protein expression in the perilesional cortex and ipsilateral hippocampus (7d to 1 month post-TBI), and ipsilateral thalamus (14d to 12 months post-TBI). In the thalamus, punctate immunoreactivity was most intense around activated microglia and mitochondria. Enzyme-linked immunoassays indicated that an acute 15% reduction, rather than an increase in plasma clusterin levels differentiated animals with TBI from sham-operated controls (AUC 0.851, p < 0.05). Our findings suggest that plasma clusterin is a candidate biomarker for acute TBI diagnosis.
Long-range propagation of protons in single-crystal VO2 involving structural transformation to HVO2
Authors: Muraoka Keita , Kanki Teruo
Published: December 2019

Vanadium dioxide (VO2) is a strongly correlated electronic material with a metal-insulator transition (MIT) near room temperature. Ion-doping to VO2 dramatically alters its transport properties and the MIT temperature. Recently, insulating hydrogenated VO2 (HVO2) accompanied by a crystal structure transformation from VO2 was experimentally observed. Despite the important steps taken towards realizing novel applications, essential physics such as the diffusion constant of intercalated protons and the crystal transformation energy between VO2 and HVO2 are still lacking. In this work, we investigated the physical parameters of proton diffusion constants accompanied by VO2 to HVO2 crystal transformation with temperature variation and their transformation energies. It was found that protons could propagate several micrometers with a crystal transformation between VO2 and HVO2. The proton diffusion speed from HVO2 to VO2 was approximately two orders higher than that from VO2 to HVO2. The long-range propagation of protons leads to the possibility of realizing novel iontronic applications and energy devices.
KCTD15 is overexpressed in human childhood B-cell acute lymphoid leukemia
Authors: Smaldone Giovanni , Beneduce Giuliana , Incoronato Mariarosaria , Pane Katia , Franzese Monica , Coppola Luigi , Cordella Angela , Parasole Rosanna , Ripaldi Mimmo , Nassa Giovanni , Soricelli Andrea , Vitagliano Luigi , Mirabelli Peppino , Salvatore Marco
Published: December 2019

Leukemic cells originate from the malignant transformation of undifferentiated myeloid/lymphoid hematopoietic progenitors normally residing in bone marrow. As the precise molecular mechanisms underlying this heterogeneous disease are yet to be disclosed, the identification and the validation of novel actors in leukemia is of extreme importance. Here, we show that KCTD15, a member of the emerging class of KCTD ((K)potassium Channel Tetramerization Domain containing) proteins, is strongly upregulated in patients affected by B-cell type acute lymphoblastic leukemia (B-ALL) and in continuous cell lines (RS4;11, REH, TOM-1, SEM) derived from this form of childhood leukemia. Interestingly, KCTD15 downregulation induces apoptosis and cell death suggesting that it has a role in cellular homeostasis and proliferation. In addition, stimulation of normal lymphocytes with the pokeweed mitogen leads to increased KCTD15 levels in a fashion comparable to those observed in proliferating leukemic cells. In this way, the role of KCTD15 is likely not confined to the B-ALL pathological state and extends to activation and proliferation of normal lymphocytes. Collectively, data here presented indicate that KCTD15 is an important and hitherto unidentified player in childhood lymphoid leukemia, and its study could open a new scenario for the identification of altered and still unknown molecular pathways in leukemia.
Maskless, rapid manufacturing of glass microfluidic devices using a picosecond pulsed laser
Authors: Wlodarczyk Krystian L. , Hand Duncan P. , Maroto-Valer M. Mercedes
Published: December 2019

Conventional manufacturing of glass microfluidic devices is a complex, multi-step process that involves a combination of different fabrication techniques, typically photolithography, chemical/dry etching and thermal/anodic bonding. As a result, the process is time-consuming and expensive, in particular when developing microfluidic prototypes or even manufacturing them in low quantity. This report describes a fabrication technique in which a picosecond pulsed laser system is the only tool required to manufacture a microfluidic device from transparent glass substrates. The laser system is used for the generation of microfluidic patterns directly on glass, the drilling of inlet/outlet ports in glass covers, and the bonding of two glass plates together in order to enclose the laser-generated patterns from the top. This method enables the manufacturing of a fully-functional microfluidic device in a few hours, without using any projection masks, dangerous chemicals, and additional expensive tools, e.g., a mask writer or bonding machine. The method allows the fabrication of various types of microfluidic devices, e.g., Hele-Shaw cells and microfluidics comprising complex patterns resembling up-scaled cross-sections of realistic rock samples, suitable for the investigation of CO2 storage, water remediation and hydrocarbon recovery processes. The method also provides a route for embedding small 3D objects inside these devices.
Individual and seasonal variation in contact rate, connectivity and centrality in red fox (Vulpes vulpes) social groups
Authors: Dorning Jo , Harris Stephen
Published: December 2019

Examining temporal variation in social connectivity and relating this to individual behaviour can help understand the role of individuals within social groups. Although red foxes are solitary foragers, they form social groups at higher population densities. To investigate the effects of season, sex and status on social connectivity in red fox social groups, we set camera traps for four consecutive seasons to record contact rates and social network metrics at food patches in seven fox territories. Higher food availability was associated with higher contact rates. Individual contact rates peaked in different seasons depending on sex and social status. Dominant foxes held central network positions in all seasons but there was no consistent pattern in social connections within territories, suggesting a greater influence of features such as group size and composition on network structure than seasonal behaviour. Increased extraterritorial movements by males during winter contributed to a significant reduction in local network connectivity. Female network strength did not vary with season, suggesting that females play an important role in maintaining year-round group cohesion. These data advance our understanding of canid social systems, the benefits of group-living in solitary foraging carnivores, and the impacts of management interventions for an ecologically important species.
Straw phytolith for less hazardous open burning of paddy straw
Authors: Nguyen Anh T. Q. , Nguyen Minh N.
Published: December 2019

Rice production helps feed at least half of the world’s population but generates approximately one billion tonnes of straw residue per annum. On-site open burning of rice straw after harvesting is common in recent times because there has been less demand for rice straw to use as fuel and fodder. Due to health and climate change concerns, open burning, which results in biomass losses, smog and emissions of green house gases, e.g., CO2, has been widely criticized and banned in many countries. Little is known about the positive benefits of straw burning, such as field care (eradication of biotic diseases) or nutrient cycling. Herein, we propose a new viewpoint in which the burning of rice straw followed by cycling of the burned materials, including silica material (so-called phytolith), into soil is demonstrated as a CO2-sequestration strategy via buffering the soil CO2 flux and coupling CO2 with the silicon cycle.
An optimized, robust and reproducible protocol to generate well-differentiated primary nasal epithelial models from extremely premature infants
Authors: Martens Anke , Amann Gabriele , Schmidt Katy , Gaupmann René , Böhm Bianca , Dehlink Eleonora , Szépfalusi Zsolt , Förster-Waldl Elisabeth , Berger Angelika , Fyhrquist Nanna , Alenius Harri , Wisgrill Lukas
Published: December 2019

Extremely premature infants are prone to severe respiratory infections, and the mechanisms underlying this exceptional susceptibility are largely unknown. Nasal epithelial cells (NEC) represent the first-line of defense and adult-derived ALI cell culture models show promising results in mimicking in vivo physiology. Therefore, the aim of this study was to develop a robust and reliable protocol for generating well-differentiated cell culture models from NECs of extremely premature infants. Nasal brushing was performed in 13 extremely premature infants at term corrected age and in 11 healthy adult controls to obtain NECs for differentiation at air-liquid interface (ALI). Differentiation was verified using imaging and functional analysis. Successful isolation and differentiation was achieved for 5 (38.5%) preterm and 5 (45.5%) adult samples. Preterm and adult ALI-cultures both showed well-differentiated morphology and ciliary function, however, preterm cultures required significantly longer cultivation times for acquiring full differentiation (44 ± 3.92 vs. 23 ± 1.83 days; p < 0.0001). Moreover, we observed that recent respiratory support may impair successful NECs isolation. Herewithin, we describe a safe, reliable and reproducible method to generate well-differentiated ALI-models from NECs of extremely premature infants. These models provide a valuable foundation for further studies regarding immunological and inflammatory responses and respiratory disorders in extremely premature infants.
Flat Band and Hole-induced Ferromagnetism in a Novel Carbon Monolayer
Authors: You Jing-Yang , Gu Bo , Su Gang
Published: December 2019

In recent experiments, superconductivity and correlated insulating states were observed in twisted bilayer graphene (TBG) with small magic angles, which highlights the importance of the flat bands near Fermi energy. However, the moiré pattern of TBG consists of more than ten thousand carbon atoms that is not easy to handle with conventional methods. By density functional theory calculations, we obtain a flat band at EF in a novel carbon monolayer coined as cyclicgraphdiyne with the unit cell of eighteen atoms. By doping holes into cyclicgraphdiyne to make the flat band partially occupied, we find that cyclicgraphdiyne with 1/8, 1/4, 3/8 and 1/2 hole doping concentration shows ferromagnetism (half-metal) while the case without doping is nonmagnetic, indicating a hole-induced nonmagnetic-ferromagnetic transition. The calculated conductivity of cyclicgraphdiyne with 1/8, 1/4 and 3/8 hole doping concentration is much higher than that without doping or with 1/2 hole doping. These results make cyclicgraphdiyne really attractive. By studying several carbon monolayers, we find that a perfect flat band may occur in the lattices with both separated or corner-connected triangular motifs with only including nearest-neighboring hopping of electrons, and the dispersion of flat band can be tuned by next-nearest-neighboring hopping. Our results shed insightful light on the formation of flat band in TBG. The present study also poses an alternative way to manipulate magnetism through doping flat band in carbon materials.
Pathological and immunological analyses of Thelohanellus kitauei (Myxozoa:Myxosporea) infection in the scattered mirror carp, Cyprinus carpio
Authors: Liu Tao , Wei Wen-Yan , Wang Kai-Yu , Yang Qian , Wang Er-Long
Published: December 2019

Thelohanellus kitauei is a spore-forming myxosporean parasite prevalent in scattered mirror carp (Cyprinus carpio) that generates numerous cysts in the intestine and causes mass mortality in fish. To investigate the infection and mortality induced by T. kitauei in pond-reared farms in Luo-Jiang (104°51’N, 31°31’E), southwest China, morphological and molecular analyses of infected fish were conducted. Natural and specific immune indicators were further evaluated to determine the immunological effects of response to parasitic infection. The infectious parasite was identified as Thelohanellus kitauei based on morphological, 18S rDNA and infectious characteristics. Scattered mirror carp was determined as the specific intermediate host of the parasite. However, T. kitauei still caused considerable damage to the fish, in particular, injury and blockage of the intestines, resulting in malnutrition and even death. The mature spores of T. kitauei colonize the intestinal submucosa of carp and form cysts of various sizes that block the intestinal tract and release spores into the enteric cavity upon rupture, leading to the next phase of T. kitauei growth. Moreover, T. kitauei-infected carp showed weaker innate immunity. IgM is involved in the fight against parasitic infection while cytokines, such as IL-6, IL-1β and TNF-α, had an impact on infection processes. To our knowledge, this is the first report to show that T. kitauei infects and causes death in scattered mirror carp. Our collective findings from systematic pathology, morphology and immunology experiments provide a foundation for further research on infections by this type of parasite and development of effective treatment strategies.
Reversibly pH-responsive gold nanoparticles and their applications for photothermal cancer therapy
Authors: Park Sanghak , Lee Woo Jin , Park Sungmin , Choi Doowon , Kim Sungjee , Park Nokyoung
Published: December 2019

Microenvironment responsive nanomaterials are attractive for therapeutic applications with regional specificity. Here we report pH responsive gold nanoparticles which are designed to aggregate in acidic condition similar to cancer environment and returned to its original disassembled states in a physiological pH. The pH responsive behavior of the particles is derived by change of electrostatic interaction among the particles where attraction and repulsion play a major role in low and high pH of the environment, respectively. Since different electrostatic interaction behavior of the particles in varied pH is induced not by irreversible chemical change but by simple protonation differences, the pH responsive process of assembly and disassembly is totally reversible. The low pH specific aggregation of gold nanoparticles resulted in red shift of plasmonic absorption peak and showed higher photothermal efficacy in acidic pH than in normal physiological pH. The low pH specific photothermal effect with long wave laser irradiation was directly applied to cancer specific photothermal therapy and resulted higher therapeutic effect for melanoma cancer cells than non-pH responsive gold nanoparticles.
Dynamic Mechanical Properties of Coals Subject to the Low Temperature-Impact Load Coupling Effect
Authors: Wang Yanbing , Yang Yang , Zhang Yuantong , Wang Jianguo
Published: December 2019

The effects of low temperature gradient on dynamic mechanical properties of coal were examined through Split-Hopkinson Pressure Bar (SHPB) Dynamic Impact Experiment, the law of dynamic mechanical parameters of coal specimen changing from room temperature to negative temperature (25 °C, −5 °C, −10 °C, −15 °C, −20 °C, −30 °C, −40 °C) was analyzed, and the coal-rock stress-strain curve characteristics subject to the low temperature-impact load coupling effect was discussed. The law of the effects of different strain rates on the rock strength properties and the compressive deformation and failure was analyzed by studying the coal specimen at −15 °C. Moreover, the mechanical properties of coal specimen in saturated and dry conditions were compared, and the effects of water and water-ice phase transition on the strength properties of the corresponding coal specimen were analyzed.
The degradation of organic compounds impacts the crystallization of clay minerals and vice versa
Authors: Jacquemot Pierre , Viennet Jean-Christophe , Bernard Sylvain , Le Guillou Corentin , Rigaud Baptiste , Delbes Ludovic , Georgelin Thomas , Jaber Maguy
Published: December 2019

Expanding our capabilities to unambiguously identify ancient traces of life in ancient rocks requires laboratory experiments to better constrain the evolution of biomolecules during advanced fossilization processes. Here, we submitted RNA to hydrothermal conditions in the presence of a gel of Al-smectite stoichiometry at 200 °C for 20 days. NMR and STXM-XANES investigations revealed that the organic fraction of the residues is no longer RNA, nor the quite homogeneous aromatic-rich residue obtained in the absence of clays, but rather consists of particles of various chemical composition including amide-rich compounds. Rather than the pure clays obtained in the absence of RNA, electron microscopy (SEM and TEM) and diffraction (XRD) data showed that the mineralogy of the experimental residues includes amorphous silica and aluminosilicates mixed together with nanoscales phosphates and clay minerals. In addition to the influence of clay minerals on the degradation of organic compounds, these results evidence the influence of the presence of organic compounds on the nature of the mineral assemblage, highlighting the importance of fine-scale mineralogical investigations when discussing the nature/origin of organo-mineral microstructures found in ancient rocks.
Development of a biodegradable polycaprolactone film incorporated with an antimicrobial agent via an extrusion process
Authors: Lyu Ji Sou , Lee Jung-Soo , Han Jaejoon
Published: December 2019

In the present study, polycaprolactone (PCL) composite films incorporated with various concentrations of grapefruit seed extract (GSE) as an antimicrobial agent were prepared using a twin-screw extruder. Physical characteristics as well as antimicrobial properties of the PCL/GSE composite films were analyzed. The results showed that the surface color of the films gradually changed with increasing GSE concentration. Fourier transform infrared spectra indicated no significant structural changes such as chemical bond formation between PCL and GSE. Thermal properties were slightly affected due to GSE incorporation. Crystallinity of the composite films decreased as the amount of GSE increased. In vitro analysis indicated that the antimicrobial activity of the PCL/GSE composite films increased as the GSE concentration increased, with a 5% concentration showing the strongest inhibitory activity against Listeria monocytogenes, with 5.8-log reduction in bacterial count. Application testing of the films was carried out for cheese packaging, and biodegradation of the samples was assessed via soil burial testing. Our findings confirmed the potential use of PCL/GSE composite films as biodegradable food packaging material with antimicrobial activity.
Specific role of N-methyl-D-aspartate (NMDA) receptor in elastin-derived VGVAPG peptide-dependent calcium homeostasis in mouse cortical astrocytes in vitro
Authors: Szychowski Konrad A. , Gmiński Jan
Published: December 2019

Under physiological and pathological conditions, elastin is degraded to produce elastin-derived peptides (EDPs). EDPs are detected in the healthy human brain, and its concentration significantly increases after ischemic stroke. Both elastin and EDPs contains replications of the soluble VGVAPG hexapeptide, which has a broad range of biological activities. Effects of VGVAPG action are mainly mediated by elastin-binding protein (EBP), which is alternatively spliced, enzymatically inactive form of the GLB1 gene. This study was conducted to elucidate the activation and role of the N-methyl-D-aspartate receptor (NMDAR) in elastin-derived VGVAPG peptide-dependent calcium homeostasis in mouse cortical astrocytes in vitro. Cells were exposed to 10 nM VGVAPG peptide and co-treated with MK-801, nifedipine, verapamil, or Src kinase inhibitor I. After cell stimulation, we measured Ca2+ level, ROS production, and mRNA expression. Moreover, the Glb1 and NMDAR subunits (GluN1, GluN2A, and GluN2B) siRNA gene knockdown were applied. We found the VGVAPG peptide causes Ca2+ influx through the NMDA receptor in mouse astrocytes in vitro. Silencing of the Glb1, GluN1, GluN2A, and GluN2B gene prevented VGVAPG peptide-induced increase in Ca2+. Nifedipine does not completely reduce VGVAPG peptide-activated ROS production, whereas MK-801, verapamil, and Src inhibitor reduce VGVAPG peptide-activated Ca2+ influx and ROS production. These data suggest the role of Src kinase signal transduction from EBP to NMDAR. Moreover, the VGVAPG peptide affects the expression of NMDA receptor subunits.
Nonreciprocal terahertz beam steering based on magneto-optic metagratings
Authors: Tan Zhiyu , Fan Fei , Dong Xipu , Cheng Jierong , Chang Shengjiang
Published: December 2019

In this work, an active nonreciprocal THz beam steering has been proposed based on a transversely magnetized metal/InSb metagrating. The nonreciprocal dispersion relation and phase shift characteristics of the metal/InSb waveguide are investigated in details. A metagrating structure with gradient phase shift has been designed based on the metal/InSb waveguide. Under the external magnetic field (EMF), the THz beam can be changed among 0, +1st, and −1st order of the metagrating. Due to the nonreciprocity of the metal/InSb metagrating, the deflection angle can be controlled by changing the positive and negative directions of the EMF, to realize bilateral symmetric scanning from −67.8° to 67.8° with over 70% diffraction efficiency, and this device also exhibits the nonreciprocal one-way transmission as an isolator with the isolation of 13 dB. This low-loss, large deflection degree, nonreciprocal beam scanner has a great potential application in the THz regime.
Fetal androgen exposure is a determinant of adult male metabolic health
Authors: Siemienowicz Katarzyna J. , Filis Panagiotis , Shaw Sophie , Douglas Alex , Thomas Jennifer , Mulroy Sally , Howie Forbes , Fowler Paul A. , Duncan W. Colin , Rae Mick T.
Published: December 2019

Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Suchin uteroandrogen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health.
Amorphous TaxMnyOz Layer as a Diffusion Barrier for Advanced Copper Interconnects
Authors: An Byeong-Seon , Kwon Yena , Oh Jin-Su , Lee Miji , Pae Sangwoo , Yang Cheol-Woong
Published: December 2019

An amorphous TaxMnyOz layer with 1.0 nm thickness was studied as an alternative Cu diffusion barrier for advanced interconnect. The thermal and electrical stabilities of the 1.0-nm-thick TaxMnyOz barrier were evaluated by transmission electron microscopy (TEM) and current density–electric field (J–E) and capacitance–voltage (C–V) measurements after annealing at 400 °C for 10 h. X-ray photoelectron spectroscopy revealed the chemical characteristics of the TaxMnyOz layer, and a tape peeling test showed that the TaxMnyOz barrier between the Cu and SiO2 layers provided better adhesion compared to the sample without the barrier. TEM observation and line profiling measurements in energy-dispersive X-ray spectroscopy after thermal annealing revealed that Cu diffusion was prevented by the TaxMnyOz barrier. Also, the J–E and C–V measurements of the fabricated metal-oxide-semiconductor sample showed that the TaxMnyOz barrier significantly improved the electrical stability of the Cu interconnect. Our results indicate that the 1.0-nm-thick TaxMnyOz barrier efficiently prevented Cu diffusion into the SiO2 layer and enhanced the thermal and electrical stability of the Cu interconnect. The improved performance of the TaxMnyOz barrier can be attributed to the microstructural stability achieved by forming ternary Ta-Mn-O film with controlled Ta/Mn atomic ratio. The chemical composition can affect the atomic configuration and density of the Ta-Mn-O film, which are closely related to the diffusion behavior. Therefore, the 1.0-nm-thick amorphous TaxMnyOz barrier is a promising Cu diffusion barrier for advanced interconnect technology.
Modified connectivity of vulnerable brain nodes in multiple sclerosis, their impact on cognition and their discriminative value
Authors: Solana Elisabeth , Martinez-Heras Eloy , Casas-Roma Jordi , Calvet Laura , Lopez-Soley Elisabet , Sepulveda Maria , Sola-Valls Nuria , Montejo Carmen , Blanco Yolanda , Pulido-Valdeolivas Irene , Andorra Magi , Saiz Albert , Prados Ferran , Llufriu Sara
Published: December 2019

Brain structural network modifications in multiple sclerosis (MS) seem to be clinically relevant. The discriminative ability of those changes to identify MS patients or their cognitive status remains unknown. Therefore, this study aimed to investigate connectivity changes in MS patients related to their cognitive status, and to define an automatic classification method to classify subjects as patients and healthy volunteers (HV) or as cognitively preserved (CP) and impaired (CI) patients. We analysed structural brain connectivity in 45 HV and 188 MS patients (104 CP and 84 CI). A support vector machine with k-fold cross-validation was built using the graph metrics features that best differentiate the groups (p < 0.05). Local efficiency (LE) and node strength (NS) network properties showed the largest differences: 100% and 69.7% of nodes had reduced LE and NS in CP patients compared to HV. Moreover, 55.3% and 57.9% of nodes had decreased LE and NS in CI compared to CP patients, in associative multimodal areas. The classification method achieved an accuracy of 74.8–77.2% to differentiate patients from HV, and 59.9–60.8% to discriminate CI from CP patients. Structural network integrity is widely reduced and worsens as cognitive function declines. Central network properties of vulnerable nodes can be useful to classify MS patients.
Expression response of chalcone synthase gene to inducing conditions and its effect on flavonoids accumulation in two medicinal species of Anoectochilus
Authors: Yang Lin , Zhang Jun Cheng , Qu Jing Tao , He Gang , Yu Hao Qiang , Li Wan Chen , Fu Feng Ling
Published: December 2019

Anoectochilus roxburghii and Anoectochilus formasanus are the major species of genus Anoectochilus used in traditional Chinese medicine for their abundant content of flavonoids and some other medicinal constituents. In recent years, their wild resources are gradually exhausted due to over-collection and ecological deterioration. Artificial cultivation and tissue culture are employed to increase production. In this study, the open reading frame, promoter and genomic sequences of the chalcone synthase (CHS) gene were cloned from these two species according to their transcriptome information, and used for expression analysis in response to the induction of phenylalanine, ultraviolet light and NaCl, and its effect investigation on accumulation of flavonoids. The results showed that the expression of the CHS genes was upregulated in response to these inductions and resulted in increasing accumulation of total flavonoids. However, the increased flavonoids induced by phenylalanine and ultraviolet light were mainly allocated into the anthocyanidin branch of flavonoids biosynthesis. Not only did it improved the medicinal value, but might have inhibitory effect on plant growth because of the increased malondialdehyde accumulation. Under the induction of appropriate concentration of NaCl, the medicinal constituents of flavonoids were increased without inhibition to plant growth.
High CD3 and ICOS and low TIM-3 expression predict favourable survival in resected oesophageal squamous cell carcinoma
Authors: Hong Min Hee , Shin Su-Jin , Shin Sung Kwan , Kim Dae Joon , Zo Jae Ill , Shim Young Mog , Lee Seung Eun , Cho Byoung Chul , Park Seong Yong , Choi Yoon-La , Kim Hye Ryun
Published: December 2019

With the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3+ TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3+ TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade.
Morphological Characteristics of Posterior Wall Fragments Associated with Acetabular Both-column Fracture
Authors: Tian Siyu , Chen Yajie , Yin Yingchao , Zhang Ruipeng , Hou Zhiyong , Zhang Yingze
Published: December 2019

Treatment of both-column fractures with posterior wall involvement is still a controversial topic. This type of posterior wall fracture is different from isolated acetabular posterior wall fracture (AO/OTA62-A1). The aim of this study is to compare the morphology of the posterior wall fragments of these two fracture patterns using computed tomography (CT) scans. All measured data were compared, and the differences between the groups (acetabular both-column fractures with posterior wall involvement were included in group A, and acetabular isolated posterior wall fractures were included in group B) were significant (P ≤ 0.05), including the direction angle, displacement, articular surface-posterior cortex ratio and articular surface area of the fracture fragment. The intraclass correlation coefficient of the measurements included inter-observer (ICC = 0.860) and intra-observer (ICC = 0.853). The morphology of the posterior wall fragments associated with both-column fractures is significantly different from that in isolated acetabular posterior wall fractures, and the treatment of the posterior wall fragment involved in both-column fractures of the acetabulum should be different from that of isolated acetabular posterior wall fractures.
Low prevalence of Borna disease virus 1 (BoDV-1) IgG antibodies in humans from areas endemic for animal Borna disease of Southern Germany
Authors: Tappe Dennis , Frank Christina , Offergeld Ruth , Wagner-Wiening Christiane , Stark Klaus , Rubbenstroth Dennis , Giese Sebastian , Lattwein Erik , Schwemmle Martin , Beer Martin , Schmidt-Chanasit Jonas , Wilking Hendrik
Published: December 2019

Borna disease virus-1 (BoDV-1) was recently discovered as cause of severe and often fatal encephalitis in humans. BoDV-1 is known to cause neurological disease in horses and sheep mainly in South and Central Germany. The virus is maintained in bicolored white-toothed shrews (Crocidura leucodon). The incidence of infection and risk factors in humans are completely unresolved. Veterinarians may be disproportionally BoDV-1-exposed through contact to animals not recognized to be BoDV-1 infected. We conducted three serosurveys predominantly in endemic areas of South Germany for the presence of BoDV-1-reactive antibodies. Anonymized residual samples from two serosurveys of veterinarians (n = 736) with interview data on exposures and one serosurvey among blood donors (n = 373) were screened with an indirect immunofluorescence antibody test, followed by a newly developed immunoblot as confirmatory assay. One serum from a 55–59-year-old veterinarian who worked in an animal practice and as a meat inspector but none from blood donors tested positive by the screening and confirmatory assays. We show that seropositive individuals are rare even in areas with highest zoonotic risk and in a group with potentially elevated exposure risk. In light of the low seroprevalence demonstrated here, the high case-fatality rate in clinically observed human BoDV-1 infections is even more impressive.
A high-sensitive sensor with HEPES-enhanced electrochemiluminescence of benzo[3]uril for Fe3+ and its application in human serum
Authors: Lei Yao , Qiu Fei , Jin Xian-Yi , Yang Jian-Mei , Liu Mao , Ge Qing-Mei , Cong Hang , Tao Zhu
Published: December 2019

An electrochemiluminescence sensor of benzo[3]uril with sensitization of HEPES was fabricated and applied for the detection of Fe3+ with high sensitivity and selectivity in human serum.
Simultaneous determination of multiclass antibiotics in sewage sludge based on QuEChERS extraction and liquid chromatography-tandem mass spectrometry
Authors: Ajibola Akinranti S. , Tisler Selina , Zwiener Christian
Published: December 2019

A QuEChERS based method with dispersive solid-phase extraction (d-SPE) clean-up followed by LC-MS-MS analysis was developed for simultaneous determination of seventeen multiclass antibiotics in sewage sludge and applied to samples from Nigeria.
A functionalized multi-walled carbon nanotube-based composite monolith as a solid-phase extraction adsorbent for on-line purification and enrichment of ursolic acid in medicinal plants
Authors: Yu Huan , Liu Haiyan , Yang Chunliu , Pang Xiaoya , Zhang Miaomiao , Yan Hongyuan , Bai Ligai , Han Dandan
Published: December 2019

A hybrid monolith was prepared and used as a sorbent for online enrichment and purification of ursolic acid from medicinal plants.
Gallium(iii)-polypyridyl complexes as anti-osteosarcoma stem cell agents
Authors: Robin Perrine , Singh Kuldip , Suntharalingam Kogularamanan
Published: December 2019

Gallium(iii) complexes with polypridyl ligands are shown to kill bulk osteosarcoma cells and osteosarcoma stem cells (OSCs) with up to nanomolar potency.
Pseudoguaianelactones A–C: three unusual sesquiterpenoids fromLindera glaucawith anti-inflammatory activities by inhibiting the LPS-induced expression of iNOS and COX-2
Authors: Ruan Qing-feng , Jiang Shi-qin , Zheng Xiao-yun , Tang Yu-qian , Yang Bao , Yi Tao , Jin Jing , Cui Hui , Zhao Zhongxiang
Published: December 2019

The pseudoguaianelactones A–C, three unusual sesquiterpenoids isolated fromLindera glauca, showed potential anti-inflammatory activities and also provide a new approach for anti-inflammatory drug discovery.
In situ fabrication of core–shell-structured Beta@Silicalite-1 catalysts by a novel steam-assisted crystallization strategy
Authors: Xu Lanjian , Yuan Yangyang , Zhang Jie , Zhang Yanfei , Zhang Xiaomin , Chen Lei , Xu Lei
Published: December 2019

A green and efficient steam-assisted crystallization (SAC) strategy was employed to synthesize a core–shell zeolite with different frameworks between the core and shell, Beta@Silicalite-1.
Recent advances in synergistic effect promoted catalysts for preferential oxidation of carbon monoxide
Authors: Jing Peng , Gong Xia , Liu Baocang , Zhang Jun
Published: December 2019

We reviewed recent advances in catalysts for PROX with emphasis on synergistic effects that contribute to enhanced catalytic performance.
Zn-Modified Co@N–C composites with adjusted Co particle size as catalysts for the efficient electroreduction of CO2
Authors: Miao Zhichao , Liu Weiqi , Zhao Yuzhen , Wang Fangyuan , Meng Jian , Liang Manfen , Wu Xiaozhong , Zhao Jinping , Zhuo Shuping , Zhou Jin
Published: December 2019

The Zn-Co@N–C composites are developed by direct annealing of Zn–Co ZIF materials. The size of Co particles could be adjusted by the introduced Zn species. The activity in CO2RR is gradually improved with the decrease of Co particle size.
Electron microscopy study of the carbon-induced 2H–3R–1T phase transition of MoS2
Authors: Macchione Micaela A. , Mendoza-Cruz Rubén , Bazán-Diaz Lourdes , Velázquez-Salazar J. Jesús , Santiago Ulises , Arellano-Jiménez María Josefina , Perez J. Francisco , José-Yacamán Miguel , Samaniego-Benitez J. Enrique
Published: December 2019

Phase transition of molybdenum disulfide (MoS2) was carried out in a pure monocrystal using a combination milling and heating process.
Localized inside-out Ostwald ripening of hybrid double-shelled cages into SnO2 triple-shelled hollow cubes for improved toluene detection
Authors: Wang Yanzhe , Liu Chunbao , Qiao Liang , Zeng Yi , Tian Hongwei , Zheng Weitao
Published: December 2019

SnO2 triple-shelled hollow cubes are prepared via extra deposition of SnO2 shell on Zn2SnO4/SnO2 double-shelled templates followed by removal of Zn2SnO4. Based on multilayer and porous configuration, their enhanced sensing properties are obtained.
Heritable nanosilver resistance in priority pathogen: a unique genetic adaptation and comparison with ionic silver and antibiotics
Authors: Valentin Elizabeth , Bottomley Amy L. , Chilambi Gayatri S. , Harry Elizabeth J. , Amal Rose , Sotiriou Georgios A. , Rice Scott A. , Gunawan Cindy
Published: December 2019

A priority pathogen is capable to evolve stable resistance characteristics that still manifest after discontinuation of the nanosilver exposure.
Hybrid polymer/porous silicon nanofibers for loading and sustained release of synthetic DNA-based responsive devices
Authors: Zuidema Jonathan M. , Bertucci Alessandro , Kang Jinyoung , Sailor Michael J. , Ricci Francesco
Published: December 2019

Synthetic DNA-based oligonucleotides are loaded into porous silicon nanoparticles and incorporated into polymer nanofibers. The functionality of these input-responsive nanodevices is retained following release from the hybrid nanofibers.
Dimers formed with the mixed-type G-quadruplex binder pyridostatin specifically recognize human telomere G-quadruplex dimers
Authors: Ma Tian-Zhu , Zhang Meng-Jia , Liao Ting-Cong , Li Jun-Hui , Zou Min , Wang Zhou-Mo , Zhou Chun-Qiong
Published: December 2019

By adjusting the length of the polyether linkers, pyridostatin (PDS) dimers displayed higher binding selectivities and thermal stabilization towards human telomere antiparallel and mixed-type G-quadruplex dimers (G2T1).
pH-Dependent morphology and optical properties of lysine-derived molecular biodynamers
Authors: Lee Sangeun , Kaya Cansu , Jang Hongje , Koch Marcus , Loretz Brigitta , Buhler Eric , Lehr Claus-Michael , Hirsch Anna Katharina Herta
Published: December 2019

The spherical micelles of the carbazole monomer transformed into nanorods in the course of the polymerization. The polymeric nanorods show pH-dependent changes in fluorescence emission and size.
Towards theoretical spectroscopy with error bars: systematic quantification of the structural sensitivity of calculated spectra
Authors: Bergmann Tobias G. , Welzel Michael O. , Jacob Christoph R.
Published: December 2019

Uncertainty quantification is applied in theoretical spectroscopy to obtain error bars accounting for the structural sensitivity of calculated spectra.