bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1
Authors: Madel Maria-Bernadette , Ibáñez Lidia , Ciucci Thomas , Halper Julia , Rouleau Matthieu , Boutin Antoine , Hue Christophe , Duroux-Richard Isabelle , Apparailly Florence , Garchon Henri-Jean , Wakkach Abdelilah , Blin-Wakkach Claudine
Published: May 2020

Bone destruction relies on interactions between bone and immune cells. Bone-resorbing osteoclasts (OCLs) were recently identified as innate immune cells activating T cells toward tolerance or inflammation. Thus, pathological bone destruction not only relies on increased osteoclast differentiation, but also on the presence of inflammatory OCLs (i-OCLs), part of which express Cx3cr1. Here, we investigated the contribution of mouse Cx3cr1+ and Cx3cr1neg i-OCLs to bone loss. We showed that Cx3cr1+ and Cx3cr1neg i-OCLs differ considerably in transcriptional and functional aspects. Cx3cr1neg i-OCLs have a high ability to resorb bone and activate inflammatory CD4+ T cells. Although Cx3cr1+ i-OCLs are associated with inflammation, they resorb less and have in vitro an immune-suppressive effect on Cx3cr1neg i-OCLs, mediated by PD-L1. Our results provide new insights into i-OCL heterogeneity. They also reveal that different i-OCL subsets may interact to regulate inflammation. This contributes to a better understanding and prevention of inflammatory bone destruction.
Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
Authors: Ramakrishnan Sathish , Bera Manindra , Coleman Jeff , Rothman James E , Krishnakumar Shyam S
Published: May 2020

Calcium (Ca2+)-evoked release of neurotransmitters from synaptic vesicles requires mechanisms both to prevent un-initiated fusion of vesicles (clamping) and to trigger fusion following Ca2+-influx. The principal components involved in these processes are the vesicular fusion machinery (SNARE proteins) and the regulatory proteins, Synaptotagmin-1 and Complexin. Here, we use a reconstituted single-vesicle fusion assay under physiologically-relevant conditions to delineate a novel mechanism by which Synaptotagmin-1 and Complexin act synergistically to establish Ca2+-regulated fusion. We find that under each vesicle, Synaptotagmin-1 oligomers bind and clamp a limited number of ‘central’ SNARE complexes via the primary interface and introduce a kinetic delay in vesicle fusion mediated by the excess of free SNAREpins. This in turn enables Complexin to arrest the remaining free ‘peripheral’ SNAREpins to produce a stably clamped vesicle. Activation of the central SNAREpins associated with Synaptotagmin-1 by Ca2+ is sufficient to trigger rapid (<100 msec) and synchronous fusion of the docked vesicles.
A critical re-evaluation of fMRI signatures of motor sequence learning
Authors: Berlot Eva , Popp Nicola J , Diedrichsen Jörn
Published: May 2020

Despite numerous studies, there is little agreement about what brain changes accompany motor sequence learning, partly because of a general publication bias that favors novel results. We therefore decided to systematically reinvestigate proposed functional magnetic resonance imaging correlates of motor learning in a preregistered longitudinal study with four scanning sessions over 5 weeks of training. Activation decreased more for trained than untrained sequences in premotor and parietal areas, without any evidence of learning-related activation increases. Premotor and parietal regions also exhibited changes in the fine-grained, sequence-specific activation patterns early in learning, which stabilized later. No changes were observed in the primary motor cortex (M1). Overall, our study provides evidence that human motor sequence learning occurs outside of M1. Furthermore, it shows that we cannot expect to find activity increases as an indicator for learning, making subtle changes in activity patterns across weeks the most promising fMRI correlate of training-induced plasticity.
ODELAM, rapid sequence-independent detection of drug resistance in isolates of Mycobacterium tuberculosis
Authors: Herricks Thurston , Donczew Magdalena , Mast Fred D , Rustad Tige , Morrison Robert , Sterling Timothy R , Sherman David R , Aitchison John D
Published: May 2020

Antimicrobial-resistant Mycobacterium tuberculosis (Mtb) causes over 200,000 deaths each year. Current assays of antimicrobial resistance need knowledge of mutations that confer drug resistance, or long periods of culture time to test growth under drug pressure. We present ODELAM (One-cell Doubling Evaluation of Living Arrays of Mycobacterium), a time-lapse microscopy-based method that observes individual cells growing into microcolonies. ODELAM enables rapid quantitative measures of growth kinetics in as little as 30 hrs under a wide variety of environmental conditions. We demonstrate ODELAM’s utility by identifying ofloxacin resistance in cultured clinical isolates of Mtb and benchmark its performance with standard minimum inhibitory concentration (MIC) assays. ODELAM identified ofloxacin heteroresistance and the presence of drug resistant colony forming units (CFUs) at 1 per 1000 CFUs in as little as 48 hrs. ODELAM is a powerful new tool that can rapidly evaluate Mtb drug resistance in a laboratory setting.
Nonalcoholic fatty liver disease, a potential risk factor of non-specific ST-T segment changes: data from a cross-sectional study
Authors: Xiao Li , Bai Tao , Zeng Junchao , Yang Rui , Yang Ling
Published: May 2020

Background

Non-specific ST-T segment changes are prevalent and are proven risk factors for early onset of cardiovascular diseases. They can increase all-cause mortality by 100∼200% and are candidate for early signs of cardiovascular changes. Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide and is one facet of a multisystem disease that confers substantial increases morbidity and mortality of nonalcoholic fatty liver-related cardiovascular diseases. It is unclear whether NAFLD is associated with non-specific ST-T changes warning early signs of cardiovascular changes. Therefore, we investigated this association.

Methods

A cross-sectional study was designed that included a sample consisting of 32,922 participants who underwent health examinations. Participants with missing information, excessive alcohol intake, viral hepatitis, chronic liver disease or established cardiovascular diseases were excluded. Electrocardiograms were used for analysis of non-specific ST-T segment changes. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis without other liver diseases. A multivariable logistic regression model was served to calculate the OR and 95% CI for non-specific ST-T segment changes.

Results

The prevalence of non-specific ST-T segment changes was 6.5% in participants with NAFLD, however, the prevalence of NAFLD was 42.9% in participants with non-specific ST-T segment changes. NAFLD was independently associated with non-specific ST-T segment changes (OR: 1.925, 95% CI: 1.727-2.143, P < 0.001). After adjusting for age, sex, heart rate, hypertension, body mass index, fasting glucose, total cholesterol, triglycerides, HDL-C, NAFLD remained an independent risk factor of non-specific ST-T segment changes (OR: 1.289, 95% CI: 1.122-1.480).

Conclusion

Non-specific ST-T segment changes were independently associated with the presence of NAFLD after adjusting for potential confounders.
Application of 16S rRNA gene sequencing in Helicobacter pylori detection
Authors: Szymczak Aleksander , Ferenc Stanisław , Majewska Joanna , Miernikiewicz Paulina , Gnus Jan , Witkiewicz Wojciech , Dąbrowska Krystyna
Published: May 2020

Helicobacter pylori is one of the major stomach microbiome components, promoting development of inflammation and gastric cancer in humans. H. pylori has a unique ability to transform into a coccoidal form which is difficult to detect by many diagnostic methods, such as urease activity detection, and even histopathological examination. Here we present a comparison of three methods for H. pylori identification: histological assessment (with eosin, hematoxylin, and Giemsa staining), polymerase chain reaction (PCR) detection of urease (ureA specific primers), and detection by 16S rRNA gene sequencing. The study employed biopsies from the antral part of the stomach (N = 40). All samples were assessed histologically which revealed H. pylori in eight patients. Bacterial DNA isolated from the bioptates was used as a template for PCR reaction and 16S rRNA gene sequencing that revealed H. pylori in 13 and in 20 patients, respectively. Thus, 16S rRNA gene sequencing was the most sensitive method for detection of H. pylori in stomach biopsy samples.
The biomarkers of key miRNAs and target genes associated with acute myocardial infarction
Authors: Wang Qi , Liu Bingyan , Wang Yuanyong , Bai Baochen , Yu Tao , Chu Xian–ming
Published: May 2020

Background

Acute myocardial infarction (AMI) is considered one of the most prominent causes of death from cardiovascular disease worldwide. Knowledge of the molecular mechanisms underlying AMI remains limited. Accurate biomarkers are needed to predict the risk of AMI and would be beneficial for managing the incidence rate. The gold standard for the diagnosis of AMI, the cardiac troponin T (cTnT) assay, requires serial testing, and the timing of measurement with respect to symptoms affects the results. As attractive candidate diagnostic biomarkers in AMI, circulating microRNAs (miRNAs) are easily detectable, generally stable and tissue specific.

Methods

The Gene Expression Omnibus (GEO) database was used to compare miRNA expression between AMI and control samples, and the interactions between miRNAs and mRNAs were analysed for expression and function. Furthermore, a protein-protein interaction (PPI) network was constructed. The miRNAs identified in the bioinformatic analysis were verified by RT-qPCR in an H9C2 cell line. The miRNAs in plasma samples from patients with AMI (n = 11) and healthy controls (n = 11) were used to construct receiver operating characteristic (ROC) curves to evaluate the clinical prognostic value of the identified miRNAs.

Results

We identified eight novel miRNAs as potential candidate diagnostic biomarkers for patients with AMI. In addition, the predicted target genes provide insight into the molecular mechanisms underlying AMI.
Dental fear association between mothers and adolescents—a longitudinal study
Authors: Wong Hai Ming , Zhang Yu Yuan , Perfecto Antonio , McGrath Colman P.J.
Published: May 2020

Aim

To assess the longitudinal association between adolescents’ and their mothers’ dental fear.

Study Design

A longitudinal questionnaire survey study.

Methods

A randomized sample of 12-year-old adolescents were selected from local Hong Kong schools. Adolescents and their mothers self-completed the Modified Dental Anxiety Scale (MDAS). The sociodemographic background of the mothers and the oral health habits of the adolescents were also collected and these measurements were repeated at 15- and 18-years-old. Non-parametric tests (Mann–Whitney U test/Kruskall Wallis test) were used to test associations between MDAS dental fear items and independent variables. Logistic regression (adjusted for family’s sociodemographic background and adolescent’s oral health habits) was performed to evaluate the longitudinal association between adolescents’ and mothers’ dental fear.

Results

A total of 212 mother-child pairs were recruited at baseline (12-year-old adolescents). In the first and second follow-ups (15- and 18-years-old), 195 and 182 mother-child pairs completed the survey. Significant associations between mother’s and child’s scores in “feeling about having their teeth scraped and polished”, “having teeth drilled”, and ‘having an injection in the gum’ were found when adolescents were 12- years-old (P < 0.01) and 18-years-old (P < 0.05), but not at 15-years-old.

Conclusion

Adolescents’ and mothers’ dental fear is associated at 12-years-old and 18-years-old, but not at 15-years-old, which is likely specific to the Hong Kong context but may be extrapolated to other industrialized countries with caution.
Components and Bioactivity of Ipomoea batatas (L.) (Sweet Potato) Ethanolic Leaf Extract
Authors: Osuntokun Oludare Temitope , Yusuf-Babatunde M. A. , Fasila Oladele, Olasumbo
Published: May 2020

Sweet potato (SP) popularly known as Ipomoea batatas, has played an important role as an energy and a phytochemical source in human nutrition and animal feeding as well as herbal medicine to treat inﬂammatory and infectious oral diseases in Nigeria. This research aims to evaluate the secondary metabolites (phytochemical), antioxidants and antimicrobial activities as well as proximate analysis and to determine the minerals content of sweet potato ethanolic leaf extracts. The screenings were performed for triterpenes, steroids, alkaloids, anthraquinones, coumarins, ﬂavonoids, saponins, tannins and phenolic acids. The color intensity of the precipitate formation was used as analytical responses to these tests. The antioxidant capacity was evaluated and antimicrobial activity was done by agar well diffusion method. The phytochemical screening showed the presence of secondary metabolites. Alkaloids, saponin, cardiac glycosides, tannin, terpenoidand steriod respectively with the following values 13.649%, 2.545 mg/g, 8.271 mg/g, 4.726 mg/g, 6.888 mg/g and 0.276%. Flavonoids were 0.852 while negative results were obtained for phlobatannin and anthraquinone. Proximate analysis of SP leaf, moisture content(MC), crude fat (CF), crude protein (CP),ash content (ASH), cured fat (CFAT) and carbohydrate(CHO) as 32.98%, 0.725%, 14.953%, 5.863%, 0.319% and 45.16%, respectively. Ca, Mg, Fe, Na and K were the mineral contents determined for SP. The zones of inhibition of bacterial growth at different concentrations (100 mg/ml, 50 mg/ml, 25 mg/ml and 12.5 mg/ml) of SP leaf extracts showed the highest antibacterial activity to Salmonella typhi with 25 mm zones of inhibition at 100 mg/ml and lowest activity to Listeria monocytogens, Staphylococcus aureus, Vibrio cholea and Pseudomonas aeruginosa all with 20 mm zones of inhibition and 12.5 mg/ml. However, the leaf extracts had the lowest antimicrobial activity to Enterrococcus faecalis, with 7 mm diameter. SP leaves demonstrated the presence of secondary metabolites with potential biological activities. Therefore it can be concluded that bioactive components and antimicrobial activity of sweet potato leaf ethanol extract against bacteria show its medicinal value and supports the widespread use of the plant as local remedy for a variety of ailment.
Line X Tester Analysis for Protein Content in Quality Protein Maize (QPM) (Zea mays L.) Genotypes
Authors: Muhammad A. , Bubuche T. S. , Mohammad I. U. , Na-Allah M. S.
Published: May 2020

Aims: To determine superior cross combination between QPM and tester (normal maize) genotypes in protein, tryptophan and lysine content so to enhanced protein content in locally adopted Maize Varieties (Tester) through Line X Tester method aimed in reducing protein deficiency in the study area and sub-Saharan Africa at large.

Study Design: Randomized Complete Block Design (RCBD) with three replicates and two border rows were used at the end of each replicate to minimize the border effect. Twenty-four 24 (12 x 2) crosses combinations were recovered through the Line X Tester Mating Method. 

Place and Duration of Study: Field trial was conducted at Jega Teaching and Research farm of Kebbi State University of Science and Technology, Aliero (KSUSTA), Kebbi State Nigeria, during 2018 and 2019 rainy seasons.

Methodology: Experimental material comprised twelve quality protein maize (QPM) (female parents), two testers (male parents or normal maize) with diverse genetic base and one check for comparison (CML312/CML442 tester A and CML202/CML395 tester B and one check Yar acre C) were grown. The emasculation was carried out where the tassels of the female plants (seed parents or line) were removed immediately as soon as appeared, through the process called detasseling and Ear where put in selfing bag for 1 to 2 days after emergence and tassels of selected male parents (Tester) were covered with waterproof selfing bag one day after emergence, pollens from tester were dusted over the silk of line and care was taken in each stage to avoid contamination of pollen grains from tagged tester with foreign pollens.

Results: Analysis of Variance revealed that, genotypes CML503 (L4 x T1) recorded highest in crude protein in a combined mean performance with 9.1% but recorded lowest lysine and tryptophan of 3.1% and 0.4% respectively and there was drastic reduction in crude protein from 2018 (9.4%) to 2019 (8.8%), lysine from 2018 (4.1%) to 2019 (3.9%) and tryptophan from 2018 (0.8%) to 2019 (0.6%), However, local check recorded an increase in crude protein, lysine and tryptophan Crude protein increased from 2018 (1.4%) to 2019 (2.4%) and in combined mean performance (5.4%), lysine also increased from 2018 (0.2%) to 2019 (0.9%) and tryptophan 2018 (0.002%) to 2019 (0.90%).

Conclusion: Study concluded that highly significant differences among genotypes indicated the presence of inherent genetic differences among treatments and hybrid of the cross between QPM CML503 and the tester-A (L4 x T1) could be used for breeding programme aimed at protein improvement and therefore, could be grown by the maize producers for crude protein, lysine and tryptophan.
Lead Adsorption onto Clay Soil Treated with Sugarcane Organic Waste Biochar
Authors: Sweed Atef A. A. , Awad Ahmed A. M.
Published: May 2020

This work aims to maximize the utilization of sugar cane cultivation and manufacture waste in Aswan Governorate, Egypt and turn it into biochar, which can be used to clean the environment from dangerous metals. Sugarcane organic wastes (filter cake, bagasse and sphere) biochars as waste bio-adsorbent materials were obtained using the pyrolysis at 350 and 700°C and 90 min residence time under limited oxygen conditions. Two batch trails were conducted to study the effects of biochar pH and shaking time on the adsorption of Pb ion from solution in precedence of soil and biochar. Models to study the kinetics of the adsorption process as pseudo-first-order and pseudo-second-order models were used.The results showed that the absorbed or precipitated (at high suspension pH) amount of Pb decreased in the order: soil treated with biochar bagasse pyrolysis at 350°C (BB350) > soil treated with biochar sphere pyrolysis at 350°C (SB350) > soil treated with biochar filter cake pyrolysis at 350°C (FB350) > soil only. At pH 9 maximum amounts of Pb of 1.794, 1.706 and 1.688 mg/g were adsorbed or precipitated on the soil treated with BB350, SB350 and FB350 respectively. However, Pb was maximum adsorbed or precipitated (1.33 mg/g) on the soil only at pH 8. The highest removal efficiency of Pb2+ from the solution was85% with treated the soil with SB350 while the lowest one was 55.5% occurred with the soil that was not treated with biochar at a shaking time of 80 minutes. The adsorption of Pb2+ by the soil in presence or absence biochars different fitted the pseudo second order kinetic model for all tested treatments (R2 ranged from 0.9901 for the soil treated with BB350 to 0.9994 for that treated with SB350).
Human Microcirculation‐on‐Chip Models in Cancer Research: Key Integration of Lymphatic and Blood Vasculatures
Authors: Luque‐González Maria Angélica , Reis Rui Luis , Kundu Subhas Chandra , Caballero David
Published: May 2020

Cancer metastasis is a highly complex and multistep process, which is initiated by the invasion of tumor cells into the microcirculation system. A diverse variety of organ‐on‐chip models are described investigating this critical event. However, most of these models solely integrate the blood vasculature and overlook the fundamental role of the lymphatic system despite the solid evidence showing that cancer cells mainly use this vascular network to initiate metastasis. Herein, the latest advances in the field of organ‐on‐chip models of the human microcirculation system in cancer research are reviewed. The reported models are employed to investigate the mechanistic determinants of tumor physiopathology and for the screening of new anticancer drugs under the scope of the microcirculation bed. Overall, the development of complete microcirculation‐on‐chip models integrating the blood and lymphatic vasculatures is expected to provide key insights into the drug delivery process, the screening of novel therapeutic compounds, or the mechanism of tumor invasion and metastasis, among others.
White Peroxidase‐Mimicking Nanozymes: Colorimetric Pesticide Assay without Interferences of O2 and Color
Authors: Liang Xin , Han Lei
Published: May 2020

Given the promising prospect of peroxidase‐like nanozymes in colorimetric assay, it is interesting and significant to eliminate their oxidase‐like activities and color interference for nanozyme‐based colorimetric assay. Here, the enzyme‐mimicking activity of GeO2 nanomaterials is discovered. GeO2 nanozymes exclusively possess peroxidase‐like activity without oxidase‐like characteristics, freeing the corresponding assay system from O2 interference. Moreover, GeO2 nanozymes are white, thereby eliminating the color interference of the nanozymes themselves in nanozymes‐based colorimetric assay. Interestingly, compared with other metal oxides, GeO2 nanozymes are easily decomposed by thiocholine, acetylcholinesterase (AChE)‐catalyzed hydrolysate, which triggers an ultrasensitive and anti‐interference organophosphate pesticides assay process based on the irreversible inhibition of AChE. The proposed strategy about finding nanozymes with single activity without interference color will open avenues for improving the performance of colorimetric analysis systems based on nanozymes.
Facet‐Dependent, Fast Response, and Broadband Photodetector Based on Highly Stable All‐Inorganic CsCu2I3 Single Crystal with 1D Electronic Structure
Authors: Li Ziqing , Li Ziliang , Shi Zhifeng , Fang Xiaosheng
Published: May 2020

Low‐dimensional metal halides at molecular level, which feature strong quantum confinement effects from intrinsic structure, are emerging as ideal candidates in optoelectronic fields. However, developing stable and nontoxic metal halides still remains a great challenge. Herein, for the first time, high‐crystalline and highly stable CsCu2I3 single crystal, which is acquired by a low‐cost antisolvent vapor assisted method, is successfully developed to construct high‐speed (trise/tdecay = 0.19 ms/14.7 ms) and UV‐to‐visible broadband (300–700 nm) photodetector, outperforming most reported photodetectors based on individual all‐inorganic lead‐free metal halides. Intriguingly, facet‐dependent photoresponse is observed for CsCu2I3 single crystal, whose morphology consists of {010}, {110}, and {021} crystal planes. The on–off ratio of {010} crystal plane is higher than that of {110} crystal plane, mainly owing to lower dark current. Furthermore, photogenerated electrons are localized in twofold chains created by [CuI4] tetrahedra, leading to relatively small effective mass and fast transport mobility along the 1D transport pathway. Anisotropic carrier transport characteristic is related to stronger confinement and higher electron density for {110} crystal planes. This work not only demonstrates the great potential of CsCu2I3 single crystal in high‐performance optoelectronics, but also gives insights into 1D electronic structure associated with fast photoresponse and high anisotropy.
Revealing the Structural Evolution of Green Rust Synthesized in Ionic Liquids by In Situ Molecular Imaging
Authors: Shen Yanjie , Fu Yao , Yao Jennifer , Lao David , Nune Satish , Zhu Zihua , Heldebrant David , Yao Xiaohong , Yu Xiao‐Ying
Published: May 2020

Ionic liquids are green solvents that have wide applications in material synthesis, catalysis, and separation. A model switchable ionic liquid (SWIL) consisting of 1,8‐diazabicycloundec‐7‐ene (DBU) and 1‐hexanol with carbon dioxide (CO2) as the trigger gas is chosen to synthesize nanocrystalline green rust. Under anoxic conditions, by adding iron (II) acetate (Fe(C2H3O2)2) and methanol to the degassed SWIL, a nanoparticulate green rust with carbonate (nano‐GR) is synthesized. More importantly, the molecular structural change of the ionic liquid resulting in green rust crystallines is first characterized using in situ liquid using time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) coupled with the system for analysis at the liquid vacuum interface (SALVI), a vacuum compatible microfluidic reactor in this work. Dimers and ionic clusters consisting ferric and ferrous ions are identified in liquid ToF‐SIMS spectra. Spectral principal component analysis is used to confirm that these ion pairs including dimers and cluster ions are different from nonionic liquids. The results show that liquid ToF‐SIMS can be a useful tool to study complex liquids at the molecular level providing insights into predicative synthesis of nanomaterials using environmentally friendly green solvents and giving unique visualization of the evolving material interface due to nucleation.
A Bias‐Free, Stand‐Alone, and Scalable Photovoltaic–Electrochemical Device for Solar Hydrogen Production
Authors: Lee Minoh , Turan Bugra , Becker Jan‐Philipp , Welter Katharina , Klingebiel Benjamin , Neumann Elmar , Sohn Yoo Jung , Merdzhanova Tsvetelina , Kirchartz Thomas , Finger Friedhelm , Rau Uwe , Haas Stefan
Published: May 2020

Although photovoltaic–electrochemical (PV–EC) water splitting is likely to be an important and powerful tool to provide environmentally friendly hydrogen, most developments in this field have been conducted on a laboratory scale so far. In order for the technology to make a sizeable impact on the energy transition, scaled up devices must be developed. Here a scalable (64 cm2 aperture area) artificial PV–EC device composed of triple‐junction thin‐film silicon solar cells in conjunction with an electrodeposited bifunctional nickel iron molybdenum water‐splitting catalyst is shown. The device shows a solar to hydrogen efficiency of up to 4.67% (5.33% active area, H2 production rate of 1.26 μmol H2/s) without bias assistance and wire connection and works for 30 min. The gas separation is enabled by incorporating a membrane in a 3D printed device frame. In addition, a wired small area device is also fabricated in order to show the potential of the concept. The device is operated for 127 h and initially 7.7% solar to hydrogen efficiency with a PV active area of 0.5 cm2 is achieved.
Recent Trends in Electrochemical Sensors for Vital Biomedical Markers Using Hybrid Nanostructured Materials
Authors: Reddy K. Koteshwara , Bandal Harshad , Satyanarayana Moru , Goud Kotagiri Yugender , Gobi Kauveri Vengatajalabathy , Jayaramudu Tippabattini , Amalraj John , Kim Hern
Published: May 2020

This work provides a succinct insight into the recent developments in electrochemical quantification of vital biomedical markers using hybrid metallic composite nanostructures. After a brief introduction to the biomarkers, five types of crucial biomarkers, which require timely and periodical monitoring, are shortlisted, namely, cancer, cardiac, inflammatory, diabetic and renal biomarkers. This review emphasizes the usage and advantages of hybrid nanostructured materials as the recognition matrices toward the detection of vital biomarkers. Different transduction methods (fluorescence, electrophoresis, chemiluminescence, electrochemiluminescence, surface plasmon resonance, surface‐enhanced Raman spectroscopy) reported for the biomarkers are discussed comprehensively to present an overview of the current research works. Recent advancements in the electrochemical (amperometric, voltammetric, and impedimetric) sensor systems constructed with metal nanoparticle‐derived hybrid composite nanostructures toward the selective detection of chosen vital biomarkers are specifically analyzed. It describes the challenges involved and the strategies reported for the development of selective, sensitive, and disposable electrochemical biosensors with the details of fabrication, functionalization, and applications of hybrid metallic composite nanostructures.
Nucleophilic Substitution Reaction of Pentafluorophenyl Aminated Perylene Diimide system with N,N‐Dimethylformamide
Authors: Wu Siyu , Yin Gengwen , Cheng Caihong , Liang Bo , Zhang Haiquan
Published: May 2020

Nucleophilic substitution process with loss of one fluorine atom was observed when pentafluorophenyl substituted benzo[ghi]perylene triimide and perylene diimide were heated in N,N‐dimethylformamide, in which N,N‐dimethylformamide acted both as solvent and nucleophile reagent. Unexpectedly, the obtained product exhibited significant intramolecular charge transfer optical properties in solutions. The mechanism of nucleophilic substitution and the influence of substituent were further studied and proposed in this manuscript.
[BO2]− as a Synthon for the Generation of Boron‐Centered Carbamate and Carboxylate Isosteres
Authors: Pécharman Anne‐Frédérique , Hill Michael S. , McMullin Claire L. , Mahon Mary F.
Published: May 2020

Oxoborane carbamate and carboxylate analogues result from the in situ trapping of [BO2]− produced by elimination of 2,3‐dimethyl‐2‐butene from a pinacolatoboryl anion.
Engineering Orthogonal Methyltransferases to Create Alternative Bioalkylation Pathways
Authors: Herbert Abigail J. , Shepherd Sarah A. , Cronin Victoria A. , Bennett Matthew R. , Sung Rehana , Micklefield Jason
Published: May 2020

S‐adenosyl‐l‐methionine (SAM)‐dependent methyltransferases (MTs) catalyse the methylation of a vast array of small metabolites and biomacromolecules. Recently, rare carboxymethylation pathways have been discovered, including carboxymethyltransferase enzymes that utilise a carboxy‐SAM (cxSAM) cofactor generated from SAM by a cxSAM synthase (CmoA). We show how MT enzymes can utilise cxSAM to catalyse carboxymethylation of tetrahydroisoquinoline (THIQ) and catechol substrates. Site‐directed mutagenesis was used to create orthogonal MTs possessing improved catalytic activity and selectivity for cxSAM, with subsequent coupling to CmoA resulting in more efficient and selective carboxymethylation. An enzymatic approach was also developed to generate a previously undescribed co‐factor, carboxy‐S‐adenosyl‐l‐ethionine (cxSAE), thereby enabling the stereoselective transfer of a chiral 1‐carboxyethyl group to the substrate.
A Three‐Dimensional Porous Organic Semiconductor Based on Fully sp2‐Hybridized Graphitic Polymer
Authors: Byun Yearin , Xie Lilia S. , Fritz Patrick , Ashirov Timur , Dincă Mircea , Coskun Ali
Published: May 2020

Dimensionality plays an important role in the charge transport properties of organic semiconductors. Although three‐dimensional semiconductors, such as Si, are common in inorganic materials, imparting electrical conductivity to covalent three‐dimensional organic polymers is challenging. Now, the synthesis of a three‐dimensional π‐conjugated porous organic polymer (3D p‐POP) using catalyst‐free Diels–Alder cycloaddition polymerization followed by acid‐promoted aromatization is presented. With a surface area of 801 m2 g−1, full conjugation throughout the carbon backbone, and an electrical conductivity of 6(2)×10−4 S cm−1 upon treatment with I2 vapor, the 3D p‐POP is the first member of a new class of permanently porous 3D organic semiconductors.
Force field in coagulation bath at low temperature induced microfibril evolution within PAN nascent fiber and precursor fiber
Authors: Gao Quan , Jing Min , Chen Meiling , Zhao Shengyao , Wang Yuxia , Qin Jianjie , Yu Meijie , Wang Chengguo
Published: May 2020

The coagulation process was vital for the microfibril evolution and mechanical properties of polyacrylonitrile (PAN) fibers. The PAN nascent fibers and precursor fibers were prepared by controlling drawing ratio of coagulation bath at low temperature during the dry‐jet wet spinning process. The microfibril morphological changes induced by force fields in coagulation bath were investigated by scanning electron microscopy and high‐resolution transmission electron microscopy. During the coagulation process, the spinning solution evolved into an interconnected network composed of random microfibrils and tie joints as a building block of the network. At low drawing ratio, the random interconnected network existed in nascent fibers. Increasing drawing ratio, the fiber filaments underwent shrinkage and the network was transformed into the transverse lamellae. Furthermore, the lamellar thickness also decreased. After the treatment of post‐spinning, similar transverse lamellae were formed in all of precursor fibers, and random microfibrillar network was stretched and oriented to develop into the aligned microfibrils in precursor fibers. The transverse fold‐chain crystal layers were densely stacked in the microfibrils. Increasing drawing ratio, the lamellae and microfibrils in precursor fibers were packed more densely and orderly. Consequently, the order and homogeneity of microfibrils in nascent fibers and precursor fibers were improved by increasing drawing ratio, which were benefit to increase fiber tensile strength and modulus.
2‐Aminoaryl‐3,5‐diaryl pyrazines: Synthesis, biological evaluation against Mycobacterium tuberculosis and docking studies
Authors: Gangarapu Nagaraja Reddy , Ranganatham Archakam , Reddy Eeda Koti , Yellappa Shivaraj , Chandrasekhar Kothapalli Bannoth
Published: May 2020

Rationally designed Mycobacterium tuberculosis (Mtb) inhibitors were synthesized under Buchwald conditions using Pd2(dba)3/xantphos and the compounds were investigated for their biological activity against the Mtb standard strain H37Rv and two other clinically isolated multidrug‐resistant strains with different drug resistance patterns. Compounds 5e, 6e, 7e, and 8e exhibited excellent antituberculosis activity against H37Rv with a minimum inhibitory concentration (MIC) value of 15 μg/ml. Compounds 5a, 6c, 7b, 8a, 8b, and 8d also displayed their potency with a MIC value in the range of 15–25 μg/ml. In addition to the Mtb studies, compounds 4e, 5e, 7e, and 8e were tested for cytotoxicity on HEK‐293 cells and compounds 7e and 8e were identified to have low toxicities of up to 200 and 300 μM, respectively. The synthesized compounds docked with the 2FUM protein of Mtb and the docking studies revealed that compounds 5e, 6e, 7e, and 8e can bind strongly in the active site of the enzyme and showed binding energies of −9.62, −10.7, −11.48, and −12.06 kcal/mol, respectively. Compound 7e forms four hydrogen bonds, whereas compound 8e forms five hydrogen bonds with amino acids, respectively. Based on these results, compounds 7e and 8e might be considered potential lead compounds with good anti‐Mtb potency.
Ozone (O3) ambient levels as a secondary airborne precursor in Fahaheel urban area, the State of Kuwait
Authors: Al‐Qassimi Masumah , Al‐Salem Sultan Majed
Published: May 2020

Two years of continuous monitoring data over two time‐spans (2004–2005 and 2014–2015) were used to investigate the relationship between ozone (O3) and nitrogen oxides (NOX ≈ NO + NO2) in Fahaheel urban area (Kuwait). Their relationship was used to understand their chemical reactions and the NO2 and O3 concentration ratio to gain an insight into the sources of total atmospheric oxides (OX = O3 + NO2) levels. A Chemical Mass Balance (CMB) model was developed to detect likely point sources around the monitoring station and quantify their contribution to the overall air pollution load. Hourly diurnal variations in O3 ground level concentrations during weekends showed a slight increase in O3 levels. In addition, it was observed that overall hourly average O3 concentration reached higher levels during weekdays and weekends in 2004–2005 compared to 2014–2015. The concentration of photochemical oxidants (e.g., O3 and NO2) can be decreased by controlling the emissions of their precursors; NOX and VOCs. The net effect of NOX emissions on O3 concentrations was negative with a weak exponential decline correlation between NOX and O3, indicating Fahaheel urban area's VOC‐sensitive characteristics. For all years considered, the slopes of the linear OX–NOX relationships were higher during daytime compared to night‐time, showing that NO2 oxidations were dominant during daytime and that O3 net production was high. The study also showed the high NOX oxidation level and the possible presence of O3 net production. The slopes during night‐time indicated that NO2 consumption exceeded its formation rate. During day and night‐time, the NO2/NOX ratio was found to decline significantly as newly emitted NOX increased, supporting the area's VOC‐sensitive nature. By setting up a CMB model around the Fahaheel receptor point, it was revealed that downstream petroleum facilities have been the major contributor to pollutants environmental load over the years.
Contextual framing of loss impacts harm avoidance during risky spatial decisions
Authors: Jarbo Kevin , Colaço David , Verstynen Timothy
Published: May 2020

Although the same decision to act can occur in multiple contexts, how these contexts differentially influence behavior is not well understood. In this paper, we investigate whether contextual framing affects individuals' behavior in spatial decision making. Although previous research suggests that individuals' judgments are sensitive to contextual (and particularly moral) factors of a scenario, no work has addressed whether this effect extends to spatial decisions. To investigate the impact of context on perceptual sensorimotor behavior, we superimposed two moral dilemmas (which we callhelpandharm) on a spatial decision‐making paradigm. The basic task required participants select a target area while avoiding an overlapping nontarget area. Although the visuospatial task was constant, the moral context was changed when participants had to execute either a drone missile strike on enemies in the harm context or deliver ammunition to allies in the help context. Participants more strongly avoided losses in the harm context, reflected by a greater selection bias away from the nontarget (i.e., allies) on drone strike trials. These findings suggest that the contextual framing of a subjective perceived loss on a spatial decision can drive avoidant motor execution behavior.
Spectrofluorometric method for the determination of ascorbic acid in pharmaceutical preparation using l‐tyrosine as fluorescence probe
Authors: Wu Yuting , Chen Qinfei , Zhao Lijun , Du Dong , Guo Nihong , Ren Haisheng , Liu Wenbin
Published: May 2020

Ascorbic acid is a vital nutrient and antioxidant that is commonly used as an additive in commercial products. Quantitation of ascorbic acid is highly desired in the medical, food, and cosmetic industries. A spectrofluorometric assay for sensitive determination of ascorbic acid was developed using l‐tyrosine as a fluorescent probe. The native fluorescence intensity of tyrosine was quenched using ascorbic acid. The linear range was 0.03–30.00 μM, and the limit of detection was 0.01 μM. The method exhibited excellent precision, accuracy, specificity, and robustness. Components of pharmaceutical preparations that are commonly found with ascorbic acid did not interfere with detection. The procedure was successfully employed for determination of ascorbic acid content in pharmaceutical tablets, injections, and nutrient supplements with satisfactory results. A Stern–Volmer plot and fluorescence lifetime revealed that quenching was attributed to the inner filter effect and static quenching. Isothermal titration calorimetry confirmed the formation of a complex between tyrosine and ascorbic acid, with a binding constant of 1.68 × 103 M−1 and reaction stoichiometry of 0.94. Thermodynamic parameters suggested spontaneous complexation via hydrophobic interactions as the dominant binding force. This method is promising for the simple and rapid determination of ascorbic in the pharmaceutical industry.
Non‐genetic biomarkers and colorectal cancer risk: Umbrella review and evidence triangulation
Authors: Zhang Xiaomeng , Gill Dipender , He Yazhou , Yang Tian , Li Xue , Monori Grace , Campbell Harry , Dunlop Malcolm , Tsilidis Konstantinos K. , Timofeeva Maria , Theodoratou Evropi
Published: May 2020

Several associations between non‐genetic biomarkers and colorectal cancer (CRC) risk have been detected, but the strength of evidence and the direction of associations are not confirmed. We aimed to evaluate the evidence of these associations and integrate results from different approaches to assess causal inference. We searched Medline and Embase for meta‐analyses of observational studies, meta‐analyses of randomized clinical trials (RCTs), and Mendelian randomization (MR) studies measuring the associations between non‐genetic biomarkers and CRC risk and meta‐analyses of RCTs on supplementary micronutrients. We repeated the meta‐analyses using random‐effects models and categorized the evidence based on predefined criteria. We described each MR study and evaluated their credibility. Seventy‐two meta‐analyses of observational studies and 18 MR studies on non‐genetic biomarkers and six meta‐analyses of RCTs on micronutrient intake and CRC risk considering 65, 42, and five unique associations, respectively, were identified. No meta‐analyses of RCTs on blood level biomarkers have been found. None of the associations were classified as convincing or highly suggestive, three were classified as suggestive, and 26 were classified as weak. For three biomarkers explored in MR studies, there was evidence of causality and seven were classified as likely noncausal. For the first time, results from both observational and MR studies were integrated by triangulating the evidence for a wide variety of non‐genetic biomarkers and CRC risk. At blood level, lower vitamin D, higher homeostatic model assessment‐insulin resistance, and human papillomavirus infection were associated with higher CRC risk while increased linoleic acid and oleic acid and decreased arachidonic acid were likely causally associated with lower CRC risk. No association was found convincing in both study types.
Improved outcomes after radiotherapy for prostate cancer: Anticoagulation, antiplatelet therapy, and platelet count as key factors in disease progression
Authors: Gutiontov Stanley I. , Choe Kevin S. , Miller Jonathan L. , Liauw Stanley L.
Published: May 2020

Background

Several studies have suggested that antiplatelet (AP) or anticoagulant (AC) therapy may improve outcome in men with prostate cancer. We evaluated the effects of AP/AC therapy and tested the hypothesis that platelet count may also be associated with outcomes.

Methods

A total of 482 patients received primary radiotherapy (median dose 72 Gy) for nonmetastatic prostate cancer; 49% received androgen deprivation therapy. NCCN risk was low/intermediate/high risk in 39%/39%/22%. AP/AC therapy and platelet counts were analyzed with respect to freedom from biochemical failure (FFBF, nadir+2), distant metastasis (FFDM), and cause specific survival (CSS).

Results

After a median follow‐up of 103 months, 10‐year FFBF, FFDM, and CSS were 77%, 92%, and 96%, respectively. The 10‐year cumulative incidence of BF and DM (with death as a competing event) was 19% and 7.0%, respectively. The 32% of men on AP/AC therapy had a lower incidence of 10‐year BF (P = .016) and a trend toward a lower incidence of DM (P = .084) and CSS (P = .091). In the entire cohort, lowest platelet quartile (platelet count <187) was associated with higher 10‐year BF (31% vs 16%, P = .0042) but not DM (9.4% vs 5.2%, P = .22) nor CSS (P = .76) compared with those patients with platelet count ≥187. AP/AC therapy was associated with a larger absolute reduction in BF for men with lowest platelet quartile (10‐year BF of 21% vs 38%, P = .092) vs platelet ≥187 (10‐year BF of 10% vs 18%, P = .053). Lowest platelet quartile remained associated with higher BF and DM on multivariable analysis controlling for risk category, WBC, and Hg.

Conclusion

AP/AC was associated with improved FFBF. Low platelet count was associated with inferior FFBF and FFDM after prostate radiotherapy. This association was tempered when antiplatelet and anticoagulant therapy was administered.
Reverse swing‐M, phase 1 study of repurposing mebendazole in recurrent high‐grade glioma
Authors: Patil Vijay M. , Bhelekar Arti , Menon Nandini , Bhattacharjee Atanu , Simha Vijai , Abhinav Ram , Abhyankar Anuja , Sridhar Epari , Mahajan Abhishek , Puranik Ameya D. , Purandare Nilendu , Janu Amit , Ahuja Ankita , Krishnatry Rahul , Gupta Tejpal , Jalali Rakesh
Published: May 2020

Background

Relapsed high‐grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in‐vitro and in‐vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma.

Methods

We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re‐irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1‐5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination.

Findings

11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%).

Interpretation

The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide‐radiation combination while the dose of 800 mg TDS needs to be used with single‐agent CCNU.
Revealing the Li2O2 Nucleation Mechanisms on CeO2 Catalysts for Lithium‐Oxygen Batteries
Authors: Cortes Henry A. , Barral María A. , Seriani Nicola , Corti Horacio R. , Vildosola Verónica L.
Published: May 2020

The addition of ceria (CeO2) nanoparticles to the cathode of a lithium‐oxygen battery results in increased capacity, lower overpotentials and better cyclability. To shed light on the mechanisms of this performance enhancement, we have investigated the early stages of Li2O2 nucleation at stoichiometric and reduced ceria surfaces by means of atomistic simulations based on density functional theory. Adsorption energies are stronger on ceria than on graphene, that is, nucleation mainly would take place on the oxide. The adsorption process of O2 is the one that determines the nucleation sites for the Li2O2 formation on the different CeO2 surfaces. The LiO2 intermediate is adsorbed at the O2 reduction sites. On the reduced (100) surface, the LiO2 tends to adsorb dissociatively, opening up the possibility to the formation of other species than the desired end‐product, Li2O2. On the contrary, optimal properties are found for the reduced (110) surface, which should therefore be the most active surface for Li2O2 nucleation among all low‐index surfaces of ceria. These findings could pave the route to produce better cathodes for Li‐oxygen batteries by the addition of carefully designed ceria nanoparticles, which maximizes the exposition of the most favorable facet.