bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of Hierarchical 2D PANI/Ni3S2 Nanosheet Arrays on Ni Foam for High‐Performance Asymmetric Supercapacitors
Authors: Cheng Qiuhui , Yang Cui , Han Lei , Tao Kai
Published: January 2020

In this work, a hierarchical 2D polyaniline (PANI)/Ni3S2 nanosheet arrays on Ni foam (NF) with open network was successfully developed by the growth of Ni3S2 nanosheet arrays derived from 2D Ni−MOF templates followed by the electrodeposition of a layer of PANI nanoflakes. The as‐prepared PANI/Ni3S2/NF was served as self‐standing supercapacitor electrode. The optimized PANI/Ni3S2/NF‐100 electrode exhibits a high areal capacity of 1.56 mA h cm−2 (487.5 mA h g−1) at 5 mA cm−2 and good rate capability (57.7 % retention at 50 mA cm−2), which significantly outperforms individual PANI/NF or Ni3S2/NF. Furthermore, an asymmetric supercapacitor fabricated by PANI/Ni3S2/NF‐100 and activated carbon electrodes can deliver a high energy density of 48.3 W h kg−1 at a power density of 799.8 W kg−1 with outstanding durability (85.7 % retention of the initial capacity) during 15000 consecutive charge‐discharge cycles. The superior electrochemical performance of PANI/Ni3S2/NF‐100 is attributed to the unique hierarchical PANI/Ni3S2 nanosheet arrays structure. Firstly, the hierarchical open network facilitates the electrolyte ions transport. Secondly, the ultrathin 2D Ni3S2 nanosheets lead to abundant electroactive sites for the Faradaic process, and the conductive PANI layer builds superb highway for fast electron transfer. Thirdly, the free‐standing electrode enables fast redox reaction and low interfacial resistance. Finally, the synergetic effect of Ni3S2 and PANI also contributes to the enhanced capacity.
Neuroprotective effects of isoquercitrin in diabetic neuropathy via Wnt/β‐catenin signaling pathway inhibition
Authors: Resham Kahkashan , Khare Pragyanshu , Bishnoi Mahendra , Sharma Shyam S.
Published: January 2020

Diabetic neuropathy is a peripheral nervous system disorder affecting both somatic and autonomic components of nervous system. A growing body of evidence have depicted that high glucose levels can induce activation of the Wnt/β‐catenin pathway, however there are no studies targeting this pathway in DN. The intent of the present study was to investigate the effects of isoquercitrin (ISQ), a Wnt/β‐catenin signaling pathway inhibitor, in diabetic neuropathy. Streptozotocin (50 mg/kg, i.p.) was used to induce diabetes in rats. 6‐week diabetic rats were treated intrathecally with ISQ at 10 and 30 μM doses for 3 days. Furthermore, to confirm the results of the intrathecal study, a 2‐week intraperitoneal treatment of ISQ was given to diabetic rats. After 6 weeks, diabetic rats developed neuropathy which was evident from reduced thermal and mechanical hyperalgesia thresholds and significant deterioration in motor nerve conduction velocity (MNCV), nerve blood flow (NBF). Sciatic nerves of diabetic neuropathy rats showed increased expression of Wnt pathway proteins namely β‐catenin, c‐myc and MMP2. Treatment with ISQ, both intrathecally (10 and 30 μM) and intraperitoneally (10 mg/kg), significantly ameliorated the alterations in behavioral pain thresholds and improved functional parameters in diabetic rats. Moreover, ISQ also downregulated the expression of Wnt/β‐catenin pathway proteins significantly in diabetic rats as compared to vehicle‐treated diabetic rats. Results of the present study suggest the neuroprotective potential of ISQ in the treatment of DN via inhibition of Wnt/β‐catenin signaling pathway.
Large‐scale expansion of feeder‐free mouse embryonic stem cells serially passaged in stirred suspension bioreactors at low inoculation densities directly from cryopreservation
Authors: Borys Breanna S. , So Tania , Roberts Erin L. , Ferrie Leah , Larijani Leila , Abraham Brett , Krawetz Roman , Rancourt Derrick E. , Kallos Michael S.
Published: January 2020

Embryonic stem cells (ESCs) have almost unlimited proliferation capacity in vitro and can retain the ability to contribute to all cell lineages, making them an ideal platform material for cell‐based therapies. ESCs are traditionally cultured in static flasks on a feeder layer of murine embryonic fibroblast cells. Although sufficient to generate cells for research purposes, this approach is impractical to achieve large quantities for clinical applications. In this study, we have developed protocols that address a variety of challenges that currently bottleneck clinical translation of ESCs expanded in stirred suspension bioreactors. We demonstrated that mouse ESCs (mESCs) cryopreserved in the absence of feeder cells could be thawed directly into stirred suspension bioreactors at extremely low inoculation densities (100 cells/ml). These cells sustained proliferative capacity through multiple passages and various reactor sizes and geometries, producing clinically relevant numbers (109 cells) and maintaining pluripotency phenotypic and functional properties. Passages were completed in stirred suspension bioreactors of increasing scale, under defined batch conditions which greatly improved resource efficiency. Output mESCs were analyzed for pluripotency marker expression (SSEA‐1, SOX‐2, and Nanog) through flow cytometry, and spontaneous differentiation and teratoma analysis was used to demonstrate functional maintenance of pluripotency.
Computational Design of Enantiocomplementary Epoxide Hydrolases for Asymmetric Synthesis of Aliphatic and Aromatic Diols
Authors: Arabnejad Hesam , Bombino Elvira , Colpa Dana I. , Jekel Peter A. , Trajkovic Milos , Wijma Hein J. , Janssen Dick B.
Published: January 2020

The use of enzymes in preparative biocatalysis often requires tailoring enzyme selectivity by protein engineering. Herein we explore the use of computational library design and molecular dynamics simulations to create variants of limonene epoxide hydrolase that produce enantiomeric diols from meso‐epoxides. Three substrates of different sizes were targeted: cis‐2,3‐butene oxide, cyclopentene oxide, and cis‐stilbene oxide. Most of the 28 designs tested were active and showed the predicted enantioselectivity. Excellent enantioselectivities were obtained for the bulky substrate cis‐stilbene oxide, and enantiocomplementary mutants produced (S,S)‐ and (R,R)‐stilbene diol with >97 % enantiomeric excess. An (R,R)‐selective mutant was used to prepare (R,R)‐stilbene diol with high enantiopurity (98 % conversion into diol, >99 % ee). Some variants displayed higher catalytic rates (kcat) than the original enzyme, but in most cases KM values increased as well. The results demonstrate the feasibility of computational design and screening to engineer enantioselective epoxide hydrolase variants with very limited laboratory screening.
Terminal Alkynes as Raman Probes of α‐Synuclein in Solution and in Cells
Authors: Flynn Jessica D. , Gimmen Megan Y. , Dean Dexter N. , Lacy Shannon M. , Lee Jennifer C.
Published: January 2020

Conformational changes in α‐synuclein (α‐syn) are central to its biological function and Parkinson's disease pathology. Here, terminal alkynes (homopropargylglycine) were employed as environmentally sensitive Raman probes at residues 1, 5, 116, and 127 to characterize soluble (disordered), micelle‐bound (α‐helical), and fibrillar (β‐sheet) α‐syn. Along with the full‐length protein, a disease‐related C‐terminal truncation (1–115) was also studied. For the first time, β‐sheet α‐syn amyloid structure was detected by the amide‐I band in N27 dopaminergic rat cells, where a reciprocal relationship between levels of fibrils and lipids was seen. Site‐specific spectral features of the terminal alkynes also revealed the heterogeneity of the cellular environment. This work shows the versatility of Raman microspectroscopy and the power of unnatural amino acids in providing structural and residue‐level insights in solution and in cells.
Recovering phosphorus as a coproduct from corn dry grind plants: A techno‐economic evaluation
Authors: Juneja Ankita , Cusick Roland , Singh Vijay
Published: January 2020

Background and objectives

The coproduct of ethanol industry, dried distiller's grains with solubles (DDGS), has phosphorus content in excess of the animal diet requirement, which leads to excess P in manure and causes environmental concerns. The objective of this study is to determine the technical and economic feasibility of recovering this excess P as a coproduct.

Findings

The amount of P was observed to reduce from 9.26 to 3.25 mg/g (db) of DDGS, which is consistent with the animal diet requirement of 3–4 mg P/g animal diet. For an existing dry grind plant of 40 million gallon ethanol capacity, an additional fixed cost of $5.7 million was estimated, with an operating cost increase of $1.29 million/year.

Conclusions

The total phosphorus recovered from the plant was estimated as 1,676 kg P/day, with an estimated operating cost of $2.33/kg P recovered.

Significance and novelty

Approximately 37 million MT of DDGS is produced annually as animal food containing excess P, which is a serious concern for the environment. This study provides with an economically feasible solution to recover the excess P as a coproduct, which has a potential to be used as fertilizer on more than 56,000 acres of land annually, growing corn and soybean.
Discovery of Structural Complexity through Self‐Assembly of Molecules Containing Rodlike Components
Authors: Zhang Ruimeng , Su Zebin , Yan Xiao‐Yun , Huang Jiahao , Shan Wenpeng , Dong Xue‐Hui , Feng Xueyan , Lin Zhiwei , Cheng Stephen Z. D.
Published: January 2020

Hierarchical structures are important for transferring and amplifying molecular functions to macroscopic properties of materials. In this regard, rodlike molecules have emerged as one of the most promising molecular building blocks to construct functional materials. Although the self‐assembly of conventional molecules containing rodlike components generally results in nematic or layered smectic phases, due to the preferred parallel arrangements of rodlike components, extensive efforts have revealed that rational molecular design provides a versatile platform to engineer rich self‐assembled structures. Herein, first successes achieved in polyphilic liquid crystals and rod–coil block systems are summarized. Special attention is paid to recent progress in the conjugation of rodlike building blocks with other molecular building blocks through the molecular Lego approach. Rod‐based giant surfactants, sphere–rod conjugates, and dendritic rodlike molecules are covered. Future perspectives of the self‐assembly of molecules containing rodlike components are also provided.
Pd‐Catalyzed Asymmetric N‐Allylation of Amino Acid Esters with Exceptional Levels of Catalyst Control: Stereo‐Divergent Synthesis of ProM‐15 and Related Bicyclic Dipeptide Mimetics
Authors: Dohmen Stephan , Reiher Martin , Albat Dominik , Akyol Sema , Barone Matthias , Neudörfl Jörg‐Martin , Kühne Ronald , Schmalz Hans‐Günther
Published: January 2020

A general and powerful method for the stereo‐controlled Pd‐catalyzed N‐allylation of amino acid esters is reported, as a previously largely unsolved synthetic challenge. Employing a new class of tartaric acid‐derived C2‐symmetric chiral diphosphane ligands the developed asymmetric amination protocol allows the conversion of various amino acid esters to the N‐allylated products with highest levels of enantio‐ or diastereoselectivity in a fully catalyst‐controlled fashion and predictable configuration. Remarkably, the in situ generated catalysts also exhibit outstanding levels of activity (ligand acceleration). The usefulness of the method was demonstrated in the stereo‐divergent synthesis of a set of new conformationally defined dipeptide mimetics, which represent new modular building blocks for the development of peptide‐inspired bioactive compounds.
Selenolysine: A New Tool for Traceless Isopeptide Bond Formation
Authors: Dardashti Rebecca Notis , Kumar Shailesh , Sternisha Shawn M. , Reddy Post Sai , Miller Brian G. , Metanis Norman
Published: January 2020

Despite their biological importance, post‐translationally modified proteins are notoriously difficult to produce in a homogeneous fashion by using conventional expression systems. Chemical protein synthesis or semisynthesis offers a solution to this problem; however, traditional strategies often rely on sulfur‐based chemistry that is incompatible with the presence of any cysteine residues in the target protein. To overcome these limitations, we present the design and synthesis of γ‐selenolysine, a selenol‐containing form of the commonly modified proteinogenic amino acid, lysine. The utility of γ‐selenolysine is demonstrated with the traceless ligation of the small ubiquitin‐like modifier protein, SUMO‐1, to a peptide segment of human glucokinase. The resulting polypeptide is poised for native chemical ligation and chemoselective deselenization in the presence of unprotected cysteine residues. Selenolysine's straightforward synthesis and incorporation into synthetic peptides marks it as a universal handle for conjugating any ubiquitin‐like modifying protein to its target.
Bis(Nitroxymethylisoxazolyl) Furoxan: A Promising Standalone Melt‐Castable Explosive
Authors: Johnson Eric C. , Sabatini Jesse J. , Chavez David E. , Wells Lucille A. , Banning Joseph E. , Sausa Rosario C. , Byrd Edward F. C. , Orlicki Joshua A.
Published: January 2020

The synthesis and crystal structure of the heterocyclic explosive bis(nitroxymethylisoxazolyl) furoxan, C10H6N6O10, are described. In addition, we report its physical properties and theoretical performance. This material was found to exhibit standalone melt‐castable explosive properties, with a melting point of 89.8 °C and an onset decomposition temperature of 193.8 °C. Bis(nitroxymethylisoxazolyl) furoxan features an insensitive behavior to impact, friction, and electrostatic discharge, with a calculated detonation pressure about 25 % higher than the state‐of‐the‐art melt‐castable explosive TNT.
Gold Nanotriangles with Crumble Topping and their Influence on Catalysis and Surface‐Enhanced Raman Spectroscopy
Authors: Liebig Ferenc , Sarhan Radwan M. , Schmitt Clemens N. Z. , Thünemann Andreas F. , Prietzel Claudia , Bargheer Matias , Koetz Joachim
Published: January 2020

By adding hyaluronic acid (HA) to dioctyl sodium sulfosuccinate (AOT)‐stabilized gold nanotriangles (AuNTs) with an average thickness of 7.5±1 nm and an edge length of about 175±17 nm, the AOT bilayer is replaced by a polymeric HA‐layer leading to biocompatible nanoplatelets. The subsequent reduction process of tetrachloroauric acid in the HA‐shell surrounding the AuNTs leads to the formation of spherical gold nanoparticles on the platelet surface. With increasing tetrachloroauric acid concentration, the decoration with gold nanoparticles can be tuned. SAXS measurements reveal an increase of the platelet thickness up to around 14.5 nm, twice the initial value of bare AuNTs. HRTEM micrographs show welding phenomena between densely packed particles on the platelet surface, leading to a crumble formation while preserving the original crystal structure. Crumbles crystallized on top of the platelets enhance the Raman signal by a factor of around 20, and intensify the plasmon‐driven dimerization of 4‐nitrothiophenol (4‐NTP) to 4,4′‐dimercaptoazobenzene in a yield of up to 50 %. The resulting crumbled nanotriangles, with a biopolymer shell and the absorption maximum in the second window for in vivo imaging, are promising candidates for biomedical sensing.
Calcium Bismuthate (CaBiO3): A Potential Sunlight‐Driven Perovskite Photocatalyst for the Degradation of Emerging Pharmaceutical Contaminants
Authors: Rokesh Karuppannan , Sakar Mohan , Do Trong‐On
Published: January 2020

This study reports the photocatalytic efficiencies of CaBiO3 (CBO) towards the degradation of contaminants of emerging concern (CEC), such as ciprofloxacin and tetracycline, under solar light irradiation. CaBiO3 was synthesized using glycine‐complexation (GC) and ion‐exchange (IE) methods. The structural difference of materials obtained by these different methods was evidenced from XRD and XPS results, and were due to the induced dual oxidation state of Bi (Bi3+/5+) in CaBiO3. The CBO synthesized by the GC method (CBO‐GC) showed a broad UV/Vis absorption range from 200 to 550 nm and a band gap energy of 2.30 eV, while it was found to be 200 to 450 nm and 2.65 eV for the CBO synthesized by the IE method (CBO‐IE). The VB potential of CBO‐IE is shifted towards more positive potentials (+2.45 eV) as compared to the CBO‐GC (+1.90 eV), and thereby the calculated CB potential of CBO‐GC and CBO‐IE was found to be −0.40 and −0.20 eV, respectively. Such positioning of the VB and CB favored the generation of highly reactive radicals towards the effective degradation of pollutants. These relative alignments of the bands could be mediated by the oxygen vacancy defects in the systems owing to the dual oxidation state of Bi. The photocurrent and impedance measurements demonstrated excellent charge separation and lower resistivity in CBO‐GC as compared to the CBO‐IE. Accordingly, the CBO‐GC showed enhanced photocatalytic degradation efficiency, improved photostability and reusability as compared to that of the CBO‐IE.
Heterochiral or Homochiral Self‐Assembly: Mercury(II), Cadmium(II), and Spontaneous Resolution of Silver(I) Complexes Derived from a Racemic Bis(pyridyl) Ligand
Authors: Huang Chao , Liu Yong‐Jie , Chen Ya‐Ting , Chen Dong‐Mei , Zhu Bi‐Xue
Published: January 2020

A novel racemic bis(pyridyl) ligand (rac‐L) was designed and synthesized by Schiff condensation reaction. Five complexes, [Hg2(LR)(LS)Cl4]·2CH3CH2OH (1), [Cd(LR)(LS)Cl2]n (2), {[Cd(LR)(LS)SO4(H2O)]·11H2O}n (3), {[Ag(LR)2]NO3·CH3CN}n (4a) and {[Ag(LS)2]NO3·CH3CN}n (4b) have been synthesized and characterized. The different geometric features of complexes 1–4 were determined by single‐crystal X‐ray diffraction. The crystal structures show that the self‐assembly with racemic ligands can lead to homochiral or heterochiral complexes, through self‐recognition or self‐discrimination of the ligand units. Complex 1 exists as a 26‐membered binuclear heterochiral macrocycle. Complexes 2 and 3 form 1D mesomeric looped chain coordination polymers with different heterochiral self‐assembly types. More interestingly, two novel 2D homochiral coordination polymers 4a and 4b were obtained as racemic conglomerates via spontaneous resolution. Furthermore, the thermal stabilities and luminescence properties of complexes 1–4 were investigated.
Hydroboration of Aldehydes, Ketones, and Carbodiimides Promoted by Mono(imidazolin‐2‐iminato) Hafnium Complexes
Authors: Khononov Maxim , Fridman Natalia , Tamm Matthias , Eisen Moris S.
Published: January 2020

Imidazolin‐2‐iminato hafnium complexes of the type [(ImRN)Hf(CH2Ph)3] were synthesized (ImtBuN = 1,3‐di‐tert‐butylimidazolin‐2‐iminato); ImDippN = 1,3‐bis(2,6‐diisopropylphenyl)‐imidazolin‐2‐iminato. The complexes were crystallized and structurally characterized. Despite the oxophilicity of the hafnium center, both hafnium complexes were catalytically active in the hydroboration of aldehydes, ketones, and carbodiimides. Herein, we present the influence of different substrates bearing electron‐withdrawing or electron‐donating groups on the catalytic reactions. Based on stoichiometric reaction in each process, plausible mechanistic scenarios are presented.
Double encapsulation of fucoxanthin using porous starch through sequential coating modification with maltodextrin and gum Arabic
Authors: Oliyaei Najme , Moosavi‐Nasab Marzieh , Tamaddon Ali Mohammad , Fazaeli Mahboubeh
Published: January 2020

This study aims to assess the effect of gum Arabic (GA), maltodextrin (MD), or their combination as a coating agent at different ratios (1/3, 1/5, and 1/7 w/w) to encapsulate fucoxanthin. For this purpose, fucoxanthin was initially extracted and purified from Sargassum angustifolium brown seaweed and then loaded into porous starch (PS). The fucoxanthin‐loaded PS samples were further contributed in another encapsulation process using the coating materials. All samples were evaluated in terms of encapsulation efficiency, Fourier‐transform infrared (FTIR) spectroscopy and stability under light, dark and low or high temperature (4 and 50°C) exposure over a certain time period. Purification of fucoxanthin was verified through HPLC and NMR spectroscopy. It was shown that the subsequent coating with MD + GA (1/7 w/w) caused an enhanced encapsulation of fucoxanthin‐loaded PS, reaching to about 96%. In addition, the stability of fucoxanthin‐loaded PS was greatly influenced by light and high temperature exposure and decreased from 85% to 58% using the GA‐coated material (1/3 w/w). First‐order kinetic model was found to be fitted well on thermal degradation data of fucoxanthin. Interestingly, the mixture of MD + GA (1/7 w/w) exhibited the highest fucoxanthin prevention at the end of the storage period. Conclusively, the findings of this study can provide simple and facile protocol for food chemists in protecting the food ingredients using encapsulation process.
Effect of Auricularia auricula aqueous extract on survival of Lactobacillus acidophilus La‐5 and Bifidobacterium bifidum Bb‐12 and on sensorial and functional properties of synbiotic yogurt
Authors: Faraki Azita , Noori Negin , Gandomi Hassan , Banuree Sayed Attaul Haq , Rahmani Fatemeh
Published: January 2020

The effect of Auricularia auricula aqueous extract (AAE) on the survival of Lactobacillus acidophilus La‐5 and Bifidobacterium bifidum Bb‐12, and on chemical and sensory properties of yogurt was investigated during 28 days of storage at 4°C. The use of 0.05% of AAE improved the survival of L. acidophilus La‐5 and B. bifidum Bb‐12 about 0.35 and 0.58 log CFU/g, respectively. However, AAE in 0.1% concentration enhanced the survival of L. acidophilus La‐5 and B. bifidum Bb‐12 about 0.43 and 0.51 log CFU/g, respectively. Moreover, 0.1% concentration of AAE drastically increased antioxidant activity and total phenolic content to 115.30 mg BHT eq./kg and 1,057.6 mg Gallic acid/kg after 28 days, respectively. Addition of AAE to the yogurt significantly decreased sensorial acceptance while increased syneresis compared to the control group (p < .05). In conclusion, the results of this study showed that addition of AAE improved probiotic protection and functional properties of the yogurt recommending its application in symbiotic yogurt.
The impact on estimations of genetic correlations by the use of super‐normal, unscreened, and family‐history screened controls in genome wide case–control studies
Authors: Kendler Kenneth S. , Chatzinakos Chris , Bacanu Silviu‐Alin
Published: January 2020

Traditionally, in normal case–control studies of disorder A, the controls are defined as those not developing the disorder. However, in genome wide association (GWA) studies, controls are sometimes (a) unscreened or (b) screened for both disorder A and disorder B, producing super‐normal controls. Using simulations, we examine how the observed genetic correlations between two disorders (A and B) are influenced by the use of unscreened, normal, and super‐normal controls. Normal controls produce unbiased estimates of the genetic correlation. However, unscreened and super‐normal controls both bias upward the genetic correlations. The strength of the bias increases with increasing population prevalences for the two disorders. With super‐normal controls, the absolute magnitude of bias is stronger when the true genetic correlation is low. The opposite is seen with the use of unscreened controls. Adding screening of first‐degree relatives of controls substantially increases the bias in genetic correlations with super‐normal controls but has minimal impact when controls are screened only for the relevant disease.
Process modifications for a hot potassium carbonate‐based CO2capture system: a comparative study
Authors: Ayittey Foster Kofi , Obek Christine Ann , Saptoro Agus , Perumal Kumar , Wong Mee Kee
Published: January 2020

Chemical absorption using hot potassium carbonate (K2CO3) is believed to be a more energy‐efficient post‐combustion CO2capture technology as compared to conventional amine‐based absorption processes. That notwithstanding, literature information on how process modifications could render this technology more appealing are limited. In this study, seven different modified process configurations have been investigated to observe their impacts on the system performances of a typical hot K2CO3‐based capture system. The results demonstrate that flue gas precooling is capable of improving the carbon removal level in the K2CO3‐based capture system by 11.46% over the base case value. This was achieved by precooling the flue gas stream from 110 to 70°C before feeding into the absorber column. Other modified process systems such as the rich solvent pre‐heating and lean vapour compression were equally observed to decrease the specific stripper reboiler duty by 24.28% and 21.38%, respectively. The findings from this research prove that process modifications are capable of enhancing the system performances of the hot K2CO3‐based post‐combustion CO2capture technology. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Astrocyte‐T cell crosstalk regulates region‐specific neuroinflammation
Authors: Williams Jessica L. , Manivasagam Sindhu , Smith Brandon C. , Sim Julia , Vollmer Lauren L. , Daniels Brian P. , Russell John H. , Klein Robyn S.
Published: January 2020

During multiple sclerosis (MS), an inflammatory and neurodegenerative disease of the central nervous system (CNS), symptoms, and outcomes are determined by the location of inflammatory lesions. While we and others have shown that T cell cytokines differentially regulate leukocyte entry into perivascular spaces and regional parenchymal localization in murine models of MS, the molecular mechanisms of this latter process are poorly understood. Here, we demonstrate that astrocytes exhibit region‐specific responses to T cell cytokines that promote hindbrain versus spinal cord neuroinflammation. Analysis of cytokine receptor expression in human astrocytes showed region‐specific responsiveness to Th1 and Th17 inflammatory cytokines. Consistent with this, human and murine astrocytes treated with these cytokines exhibit differential expression of the T cell localizing molecules VCAM‐1 and CXCR7 that is both cytokine and CNS region‐specific. Using in vivo models of spinal cord versus brain stem trafficking of myelin‐specific T cells and astrocyte‐specific deletion strategies, we confirmed that Th1 and Th17 cytokines differentially regulate astrocyte expression of VCAM‐1 and CXCR7 in these locations. Finally, stereotaxic injection of individual cytokines into the hindbrain or spinal cord revealed region‐ and cytokine‐specific modulation of localizing cue expression by astrocytes. These findings identify a role for inflammatory cytokines in mediating local astrocyte‐dependent mechanisms of immune cell trafficking within the CNS during neuroinflammation.
Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis
Authors: Sridhar Siddharth , Yip Cyril Chik‐Yan , Wu Shusheng , Chew Nicholas Foo‐Siong , Leung Kit‐Hang , Chan Jasper Fuk‐Woo , Zhao Pyrear Suhui , Chan Wan‐Mui , Poon Rosana Wing‐Shan , Tsoi Hoi‐Wah , Cai Jian‐Piao , Chan Helen Shuk‐Ying , Leung Anthony Wai‐Shing , Tse Cindy Wing‐Sze , Zee Jonpaul Sze‐Tsing , Tsang Owen Tak‐Yin , Cheng Vincent Chi‐Chung , Lau Susanna Kar‐Pui , Woo Patrick Chiu‐Yat , Tsang Dominic Ngai‐Chong , Yuen Kwok‐Yung
Published: January 2020

Background and Aims

Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV‐A). HEV species C genotype 1 (HEV‐C1) circulates in rats and is highly divergent from HEV‐A. It was previously considered unable to infect humans, but the first case of human HEV‐C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong.

Approach and Results

We conducted a territory‐wide prospective screening study for HEV‐C1 infection over a 31‐month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV‐C1 RNA. In addition, 186 captured commensal rats were screened for HEV‐C1 RNA. Sequences of human‐derived and rat‐derived HEV‐C1 isolates were compared. Epidemiological and clinical features of HEV‐C1 infection were analyzed. HEV‐C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV‐C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV‐C1 was detected in cerebrospinal fluid. HEV‐C1 hepatitis was generally milder than HEV‐A hepatitis. HEV‐C1 RNA was detected in 7/186 (3.76%) rats. One HEV‐C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain.

Conclusions

HEV‐C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV‐C1 infection and extrahepatic manifestations. Subclinical HEV‐C1 infection threatens blood safety. Tests for HEV‐C1 are required in clinical laboratories.
Bespoken Nanoceria: An Effective Treatment in Experimental Hepatocellular Carcinoma
Authors: Fernández‐Varo Guillermo , Perramón Meritxell , Carvajal Silvia , Oró Denise , Casals Eudald , Boix Loreto , Oller Laura , Macías‐Muñoz Laura , Marfà Santi , Casals Gregori , Morales‐Ruiz Manuel , Casado Pedro , Cutillas Pedro R. , Bruix Jordi , Navasa Miquel , Fuster Josep , Garcia‐Valdecasas Juan Carlos , Pavel Mihai C. , Puntes Víctor , Jiménez Wladimiro
Published: January 2020

Background and Aims

Despite the availability of new‐generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer‐related deaths worldwide. Cerium oxide nanoparticles (CeO2NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti‐inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2NPs as therapeutic agents in HCC.

Approach and Results

HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2NPs on tumor progression and animal survival was investigated. Hepatic tissue MS‐based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2NPs decreased phosphatidylcholine‐derived arachidonic acid and reverted the HCC‐induced increase of linoleic acid in several lipid components. Furthermore, CeO2NPs reduced serum alpha‐protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated.

Conclusions

These data indicate that CeO2NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC.
Synthesis and characterization of thiol‐acrylate hydrogels using a base‐catalyzed Michael addition for 3D cell culture applications
Authors: Khan Anowar H. , Cook Jeffery K. , Wortmann Wayne J. , Kersker Nathan D. , Rao Asha , Pojman John A. , Melvin Adam T.
Published: January 2020

There is significant interest in developing new approaches for culturing mammalian cells in a three‐dimensional (3D) environment due to the fact that it better recapitulates the in vivo environment. The goal of this work was to develop thiol‐acrylate, biodegradable hydrogels that possess highly tunable properties to support in vitro 3D culture. Six different hydrogel formulations were synthesized using two readily available monomers, a trithiol (ETTMP 1300 [ethoxylated trimethylolpropane tri(3‐mercaptopropionate) 1300]) and a diacrylate (PEGDA 700 [polyethylene glycol diacrylate 700]), polymerized by a base‐catalyzed Michael addition reaction. The resultant hydrogels were homogeneous, hydrophilic, and biodegradable. Different mechanical properties such as gelation time, storage modulus (or the elasticity G'), swelling ratio, and rate of degradation were tuned by varying the weight percentage of polymer, the molar ratio of thiol‐to‐acrylate groups, and the pH of the solution. Cytocompatibility was assessed using two model breast cancer cell lines by both 2D and 3D cell culturing approaches. The hydrogel formulations with a thiol‐to‐acrylate molar ratio of 1.05 were found to be optimal for both 2D and 3D cultures with MDA‐MB‐231 cellular aggregates found to be viable after 17 days of 3D continuous culture. Finally, MCF7 cells were observed to form 3D spheroids up to 600 μm in diameter as proof of principle for the thiol‐acrylate hydrogel to function as a scaffold for in vitro 3D cell culture. A comparison of the different mechanical properties of the six hydrogel formulations coupled with in vitro cell culture results and findings from previously published hydrogels conclude that the thiol‐acrylate hydrogels have significant potential as a scaffold for 3D cell culture.
Exosomes from CD133+ cells carrying circ‐ABCC1 mediate cell stemness and metastasis in colorectal cancer
Authors: Zhao Hong , Chen Shixia , Fu Qiang
Published: January 2020

Colorectal cancer (CRC), a fatal tumor, has been diagnosed as one of the most prevalent types of cancers globally, inducing multiple cancer‐linked deaths. Mounting evidence has revealed that circular RNA (circRNA) elicits a regulatory impact on the initiation and development of cancers. Emerged as a new circRNA, hsa_circ_0000677 (circ‐ABCC1) has not been studied in cancer progression. This study is the first attempt to explore the regulatory role of circ‐ABCC1 in CRC. In this study, data from sphere‐forming, transwell, and Western blot analyses revealed that cell stemness, sphere formation, and metastasis were notably enhanced in CD133+ cells isolated from CRC cells. In addition, exosomes from CD133+ cells could promote cell stemness, sphere formation, and metastasis. Moreover, circ‐ABCC1 was verified to be characterized with a loop structure through quantitative reverse‐transcription polymerase chain reaction analysis. Functional assays testified that the upregulation of circ‐ABCC1 contributed to cell stemness, sphere formation, and metastasis in CD133−/Caco2 or CD133−/HCT15 cells. Furthermore, the interaction between circ‐ABCC1 and β‐catenin was analyzed via RNA immunoprecipitation and RNA pull‐down and finally, circ‐ABCC1 was confirmed to facilitate CRC progression by activating the Wnt/β‐catenin pathway. To sum up, exosomes from CD133+ cells carrying circ‐ABCC1 can mediate cell stemness and metastasis in CRC, unveiling that circ‐ABCC1 serves as a novel candidate target for CRC treatment.
Crizotinib sensitizes the erlotinib resistant HCC827GR5 cell line by influencing lysosomal function
Authors: Van Der Steen Nele , Keller Kaylee , Dekker Henk , Porcelli Letizia , Honeywell Richard J. , Van Meerloo Johan , Musters René J. P. , Kathmann Ietje , Frampton Adam E. , Liu Daniel S. K. , Ruijtenbeek Rob , Rolfo Christian , Pauwels Patrick , Giovannetti Elisa , Peters Godefridus J.
Published: January 2020

In non‐small cell lung cancer, sensitizing mutations in epidermal growth factor receptor (EGFR) or cMET amplification serve as good biomarkers for targeted therapies against EGFR or cMET, respectively. Here we aimed to determine how this different genetic background would affect the interaction between the EGFR‐inhibitor erlotinib and the cMET‐inhibitor crizotinib. To unravel the mechanism of synergy we investigated the effect of the drugs on various parameters, including cell cycle arrest, migration, protein phosphorylation, kinase activity, the expression of drug efflux pumps, intracellular drug concentrations, and live‐cell microscopy. We observed additive effects in EBC‐1, H1975, and HCC827, and a strong synergism in the HCC827GR5 cell line. This cell line is a clone of the HCC827 cells that harbor an EGFR exon 19 deletion and has been made resistant to the EGFR‐inhibitor gefitinib, resulting in cMET amplification. Remarkably, the intracellular concentration of crizotinib was significantly higher in HCC827GR5 compared to the parental HCC827 cell line. Furthermore, live‐cell microscopy with a pH‐sensitive probe showed a differential reaction of the pH in the cytoplasm and the lysosomes after drug treatment in the HCC827GR5 in comparison with the HCC827 cells. This change in pH could influence the process of lysosomal sequestration of drugs. These results led us to the conclusion that lysosomal sequestration is involved in the strong synergistic reaction of the HCC827GR5 cell line to crizotinib–erlotinib combination. This finding warrants future clinical studies to evaluate whether genetic background and lysosomal sequestration could guide tailored therapeutic interventions.
circRNA‐14723 promotes hepatocytes proliferation in rat liver regeneration by sponging rno‐miR‐16‐5p
Authors: Guo Xueqiang , Xi Lingling , Li Lifei , Guo Jianlin , Jin Wei , Chang Cuifang , Zhang Jingbo , Xu Cunshuan , Chen Guangwen
Published: January 2020

Circular RNA (circRNA) is a subclass of noncoding RNA (ncRNA) detected within mammalian tissues and cells. However, its regulatory role during the proliferation phase of rat liver regeneration (LR) remains unreported. This study was designed to explore their regulatory mechanisms in cell proliferation of LR. The circRNA expression profile was detected by high‐throughput sequencing. It was indicated that 260 circRNAs were differentially expressed during the proliferation phase of rat LR. Among them, circ‐14723 displayed a significantly differential expression. We further explored its regulatory mechanism in rat hepatocytes (BRL‐3A cells). First, EdU, flow cytometry and western blot (WB) indicated that knocking down circ‐14723 inhibited BRL‐3A cells proliferation. Second, RNA‐Pulldown and dual‐luciferase report assay showed that circ‐14723 could sponge rno‐miR‐16‐5p. At last, WB showed that the reported target genes of rno‐miR‐16‐5p, CCND1, and CCNE1 were downregulated after knocking down circ‐14723. In conclusion, we found that circ‐14723 exerted a critical role in G1/S arrest to promote cell proliferation via rno‐miR‐16‐5p/CCND1 and CCNE1 axis in rat LR. This finding further revealed the regulatory mechanisms of circRNA on cell proliferation of LR, and might provide a potential target for clinical problems.
Retracted: LINC00449 regulates the proliferation and invasion of acute monocytic leukemia and predicts favorable prognosis
Authors: Shi Yuan , Zhu Yuandong , Zheng Xiao , Zheng Zhuojun
Published: January 2020

Acute myeloid leukemia (AML) is a highly aggressive disease that causes high mortality. Long noncoding RNA (lncRNA) have studied in recent years that could be a potential biomarker and therapeutic target. Therefore, it is urgently necessary to explore the novel lncRNAs in AML. Microarray analysis was performed to determine the differentially expressed lncRNAs between mononuclear cells of AML and normal samples. The biological function of lncRNA on cell proliferation and migration was measured in vitro. The predicted downstream target of lncRNA was validated by dual‐luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, and rescue experiments. The tumor formation and metastasis study were conducted in vivo. The expression of lncRNA in clinical samples was determined by a quantitative reverse transcription‐polymerase chain reaction. LINC00449 was one of the most differentially expressed lncRNA which is mainly located in the cytoplasm. We found that overexpression of LINC00449 could inhibit the cell proliferation and invasion of AML cells in vitro and in vivo. Besides, miR‐150 was identified as the downstream target gene that was negatively regulated by LINC00449 and FOXD3 was targeted by miR‐150. The results were confirmed by dual‐luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, rescue experiments, and in vivo assays. Patients with AML with high expression of LINC0049 may characterize a favorable survival. All the above‐mentioned findings indicated that the LINC00449/miR‐150/FOXD3 signaling pathway might represent a novel prognostic biomarker or therapeutic target for the treatment of AML.
PD‐1/PD‐L1‐dependent immune response in colorectal cancer
Authors: Payandeh Zahra , Khalili Saeed , Somi Mohammad Hossein , Mard‐Soltani Maysam , Baghbanzadeh Amir , Hajiasgharzadeh Khalil , Samadi Nasser , Baradaran Behzad
Published: January 2020

Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.
Endoplasmic reticulum distribution during bovine oocyte activation is regulated by protein kinase C via actin filaments
Authors: Feitosa Weber Beringui , Lopes Everton , Visintin Jose Antonio , Assumpção Mayra Elena Ortiz D'Avila
Published: January 2020

Fertilization‐induced [Ca2+]i oscillations generally depend on the release of calcium ions from the endoplasmic reticulum (ER). Since ER is the main store of calcium ions, it plays an important role in oocyte fertilization. However, the mechanism of ER organization at oocyte activation is unknown. Here, we show that protein kinase C (PKC) is involved in ER distribution during bovine oocyte activation, but not involved in cell cycle resumption and spindle organization. Actin filaments were affected by PKC pharmacological inhibition. In addition, similar to PKC results, the actin‐depolymerizing drug cytochalasin B affected the ER distribution during oocyte activation. Specifically, we have demonstrated that ER organization during bovine oocyte activation is regulated by PKC possibly through its action on actin filaments regulation. Taken together, the results presented here provide further information on the pathway involved in the regulation of ER organization during oocyte activation and new insight into the functional role of PKC and actin filaments during this process.
Anatomy, micromorphology, and histochemistry of leaves and stems of Cantinoa althaeifolia (Lamiaceae)
Authors: de Almeida Valter Paes , Raman Vijayasankar , Raeski Paola Aparecida , Urban Amanda Migliorini , Swiech Juliane Nadal , Miguel Marilis Dallarmi , Farago Paulo Vitor , Khan Ikhlas Ahmed , Budel Jane Manfron
Published: January 2020

This article enumerates the detailed anatomy of Cantinoa althaeifolia (Lamiaceae) illustrated with light and scanning electron microscopy images. The anatomical markers include the presence of branched nonglandular trichomes and capitate, peltate, and clavate types of glandular trichomes; prismatic crystals on the leaf and stem surfaces; and oil droplets in the leaf mesophyll. Histochemical tests and EDS analyses were performed in order to detect the composition of certain cells and their contents. The key findings of the present study can contribute to the taxonomy, species identification, and quality control of Cantinoa althaeifolia.
Linkages to HIV confirmatory testing and antiretroviral therapy after online, supervised, HIV self‐testing among Thai men who have sex with men and transgender women
Authors: Phanuphak Nittaya , Jantarapakde Jureeporn , Himmad Linrada , Sungsing Thanthip , Meksena Ratchadaporn , Phomthong Sangusa , Phoseeta Petchfa , Tongmuang Sumitr , Mingkwanrungruang Pravit , Meekrua Dusita , Sukthongsa Supachai , Hongwiangchan Somporn , Upanun Nutchanin , Jirajariyavej Supunnee , Jadwattanakul Tanate , Barisri Supphadith , Pankam Tippawan , Phanuphak Praphan
Published: January 2020

Introduction

Online, supervised, HIV self‐testing has potential to reach men who have sex with men (MSM) and transgender women (TGW) who never tested before and who had high HIV‐positive yield. We studied linkages to HIV confirmatory test and antiretroviral therapy (ART) initiation among Thai MSM and TGW who chose online and/or offline platforms for HIV testing and factors associated with unsuccessful linkages.

Methods

MSM and TGW were enrolled from Bangkok Metropolitan Region and Pattaya during December 2015 to June 2017 and followed for 12 months. Participants could choose between: 1) offline HIV counselling and testing (Offline group), 2) online pre‐test counselling and offline HIV testing (Mixed group) and 3) online counselling and online, supervised, HIV self‐testing (Online group). Sociodemographic data, risk behaviour and social network use characteristics were collected by self‐administered questionnaires. Linkages to HIV confirmatory testing and/or ART initiation were collected from participants who tested reactive/positive at baseline and during study follow‐up. Modified Poisson regression models identified covariates for poor retention and unsuccessful ART initiation.

Results

Of 465 MSM and 99 TGW, 200 self‐selected the Offline group, 156 the Mixed group and 208 the Online group. The Online group demonstrated highest HIV prevalence (15.0% vs. 13.0% vs. 3.4%) and high HIV incidence (5.1 vs. 8.3 vs. 3.2 per 100 person‐years), compared to the Offline and Mixed groups. Among 60 baseline HIV positive and 18 seroconversion participants, successful ART initiation in the Online group (52.8%) was lower than the Offline (84.8%) and Mixed groups (77.8%). Factors associated with unsuccessful ART initiation included choosing to be in the Online group (aRR 3.94, 95% CI 1.07 to 14.52), <17 years old at first sex (aRR 3.02, 95% CI 1.15 to 7.92), amphetamine‐type stimulants use in the past six months (aRR 3.6, 95% CI 1.22 to 10.64) and no/single sex partner (aRR 3.84, 95%CI 1.36 to 10.83) in the past six months.

Conclusions

Online, supervised, HIV self‐testing allowed more MSM and TGW to know their HIV status. However, linkages to confirmatory test and ART initiation once tested HIV‐reactive are key challenges. Alternative options to bring HIV test confirmation, prevention and ART services to these individuals after HIV self‐testing are needed.