bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence Investigation of NMC Cathode Manufacturing Parameters Interdependencies
Authors: Cunha Ricardo Pinto , Lombardo Teo , Primo Emiliano N. , Franco Alejandro A.
Published: November 2019

The number of parameters involved in lithium‐ion battery electrode manufacturing and the complexity of the physicochemical interactions throughout the associated processes make highly complex to find interdependencies between the final electrode characteristics and the fabrication parameters. In this work, we have analyzed three different machine‐learning algorithms (decision tree, support vector machine, and deep neural network) in order to find the best one to uncover the interdependencies between the slurry manufacturing parameters and the final properties of NMC‐based cathodes. The results revealed that the support vector machine method shows high accuracy and the possibility to predict the influence of manufacturing parameters on themass loading and porosity of the electrodes in a straightforward graphical way. Furthermore, we report for the first time this new approach and a case study that, by comparing the trends observed experimentally and from the model, demonstrates the validity and the quality of the proposed approach.
Resting‐state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain
Authors: Cho Shinho , Hachmann Jan T. , Balzekas Irena , In Myung‐Ho , Andres‐Beck Lindsey G. , Lee Kendall H. , Min Hoon‐Ki , Jo Hang Joon
Published: November 2019

Introduction

While the clinical efficacy of deep brain stimulation (DBS) the treatment of motor‐related symptoms is well established, the mechanism of action of the resulting cognitive and behavioral effects has been elusive.

Methods

By combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood‐oxygenation‐level‐dependent (BOLD) signal changes induced by stimulating the nucleus accumbens in a large animal model.

Results

We found that diffused BOLD activation across multiple functional networks, including the prefrontal, limbic, and thalamic regions during the stimulation, resulted in a significant change in inter‐regional functional connectivity. More importantly, the magnitude of the modulation was closely related to the strength of the inter‐regional resting‐state functional connectivity.

Conclusions

Nucleus accumbens stimulation affects the functional activity in networks that underlie cognition and behavior. Our study provides an insight into the nature of the functional connectivity, which mediates activation effect via brain networks.
Reversible Phase Transition of Porous Coordination Polymers
Authors: Fan Wen‐Wen , Cheng Yi , Zheng Li‐Yan , Cao Qiu‐E.
Published: November 2019

Porous coordination polymers or metal–organic frameworks with reversible phase‐transition behavior possess some attractive properties, and can respond to external stimuli, including physical and chemical stimuli, in a dynamic fashion. Their phase transitions can be triggered by adsorption/desorption of guest molecules, temperature changes, high pressure, light irradiation, and electric fields; these mainly include two types of transitions: crystal–amorphous and crystal–crystal transitions. These types of porous coordination polymers have received much attention because of their interesting properties and potential applications. Herein, reversible phase transition porous coordination polymers are summarized and classified based on different stimuli sources. Corresponding typical examples are then introduced. Finally, examples of their applications in gas separation, chemical sensors, guest molecule encapsulation, and energy storage are also presented.
Bridging and Conformational Control of Porphyrin Units through Non‐Traditional Rigid Scaffolds
Authors: Grover Nitika , Locke Gemma M. , Flanagan Keith J. , Beh Michael H. R. , Thompson Alison , Senge Mathias O.
Published: November 2019

Connecting two porphyrin units in a rigid linear fashion, without any undesired electron delocalization or communication between the chromophores, remains a synthetic challenge. Herein, a broad library of functionally diverse multi‐porphyrin arrays that incorporate the non‐traditional rigid linker groups cubane and bicyclo[1.1.1]pentane (BCP) is described. A robust, reliable, and versatile synthetic procedure was employed to access porphyrin‐cubane/BCP‐porphyrin arrays, representing the largest non‐polymeric structures available for cubane/BCP derivatives. These reactions demonstrate considerable substrate scope, from utilization of small phenyl moieties to large porphyrin rings, with varying lengths and different angles. To control conformational flexibility, amide bonds were introduced between the bridgehead carbon of BCP/cubane and the porphyrin rings. Through varying the orientation of the substituents around the amide bond of cubane/BCP, different intermolecular interactions were identified through single crystal X‐ray analysis. These studies revealed non‐covalent interactions that are the first‐of‐their‐kind including a unique iodine‐oxygen interaction between cubane units. These supramolecular architectures indicate the possibility to mimic a protein structure due to the sp3 rigid scaffolds (BCP or cubane) that exhibit the essential conformational space for protein function while simultaneously providing amide bonds for molecular recognition.
Development of a Library of Thiophene‐Based Drug‐Like Lego Molecules: Evaluation of Their Anion Binding, Transport Properties, and Cytotoxicity
Authors: Vieira Paulo , Miranda Margarida Q. , Marques Igor , Carvalho Sílvia , Chen Li‐Jun , Howe Ethan N. W. , Zhen Carl , Leung Claudia Y. , Spooner Michael J. , Morgado Bárbara , da Cruz e Silva Odete A. B. , Moiteiro Cristina , Gale Philip A. , Félix Vítor
Published: November 2019

The anion‐binding and transport properties of an extensive library of thiophene‐based molecules are reported. Seventeen bis‐urea positional isomers, with different binding conformations and lipophilicities, have been synthesized by appending α‐ or β‐thiophene or α‐, β‐, or γ‐benzo[b]thiophene moieties to an ortho‐phenylenediamine central core, yielding six subsets of positional isomers. Through 1H NMR, X‐ray crystallography, molecular modelling, and anion efflux studies, it is demonstrated that the most active transporters adopt a pre‐organized binding conformation capable of promoting the recognition of chloride, using urea and C−H binding groups in a cooperative fashion. Additional large unilamellar vesicle‐based assays, carried out under electroneutral and electrogenic conditions, together with N‐methyl‐d‐glucamine chloride assays, have indicated that anion efflux occurs mainly through an H+/Cl− symport mechanism. On the other hand, the most efficient anion transporter displays cytotoxicity against tumor cell lines, while having no effects on a cystic fibrosis cell line.
Cell‐Encapsulating Hydrogel Puzzle: Polyrotaxane‐Based Self‐Healing Hydrogels
Authors: Cho Ik Sung , Ooya Tooru
Published: November 2019

Slide‐ring hydrogels using polyrotaxanes have been developed as highly tough soft materials. However, they have never been used as biomaterials because of the lack of biocompatibility. Meanwhile, self‐healing hydrogels are expected to improve fatigue resistance and extend the period of use. However, owing to the lack of high mechanical strength, they are limited in their use as biomaterials. Here we first developed a biocompatible self‐healing/slide‐ring hydrogel using glycol chitosan and a water‐soluble polyrotaxane. We obtained excellent mechanical toughness and biocompatibility to promote the proliferation of human umbilical vein endothelial cells (HUVECs) encapsulated in the hydrogel. Owing to the rapid self‐healing property, the cell‐encapsulating gels adjusted arbitrarily, maintaining good cell proliferation function. Therefore, slide‐ring hydrogels enable the use of biomaterials for soft‐tissue engineering.
Microporous Carbon Nanofibers Derived from Poly(acrylonitrile‐co‐acrylic acid) for High‐Performance Supercapacitors
Authors: Li Jiye , Song Xin , Zhang Weimiao , Xu Hao , Guo Teng , Zhang Xu , Gao Jiefeng , Pang Huan , Xue Huaiguo
Published: November 2019

Carbon nanofiber (CNF)‐based supercapacitors have promising applications in the field of energy storage. It is desirable, but remains challenging, to develop CNF electrode materials with large specific surface area (SSA), high specific capacitance (SC), and high power density, as well as excellent cycling stability and high reliability. Herein, acrylonitrile–acrylic acid copolymer P(AN‐co‐AA) was synthesized for the preparation of nitrogen‐doped microporous CNFs. Thermal degradation of the AA segment leads to the formation of micropores that are distributed not only on the CNF surface, but also inside the material. The microporous structure and nitrogen content can be manipulated at the molecular level by adjusting the weight ratio between AN and AA, and the SSA and SC could reach as high as 1099 m2 g−1 and 156 F g−1, respectively. After KOH activation, the activated CNFs have an extremely high SSA of 2117 m2 g−1 and SC of 320 F g−1, which are among the highest values ever reported for electric double‐layer supercapacitors with an alkaline electrolyte. Furthermore, the capacitance retention, which can be maintained at 99 % even after 16 000 cyclic tests, reveals outstanding durability and repeatability.
Electronic Metal‐Support Interaction‐Modified Structures and Catalytic Activity of CeOx Overlayers in CeOx/Ag Inverse Catalysts
Authors: Ren Muqing , Qian Kun , Huang Weixin
Published: November 2019

Invited for the cover of this issue is Weixin Huang and co‐workers at the University of Science and Technology of China. The image depicts the strong influence of electronic metal‐support interaction (EMSI) on electronic structures and the catalytic activity of CeOx
/Ag inverse catalysts. Read the full text of the article at 10.1002/chem.201904134.
Non‐stochastic behavior in sodium chlorate crystallization
Authors: Cruz José‐Manuel , Hernández‐Lechuga Karem , Domínguez‐Valle Israel , Fuentes‐Beltrán Alejandro , Sánchez‐Morales Javier Ulises , Ocampo‐Espindola Jorge Luis , Polanco Carlos , Micheau Jean‐Claude , Buhse Thomas
Published: November 2019

NaClO3 is achiral in solution. If crystallization is performed under a static set‐up, it is recognized that the stochastic nucleation probability results in a racemic mixture of the conglomerate. In this paper, we report a reexamination of the crystallization of NaClO3 from static solution in petri dishes that was conducted over a number of years and is based on the count and analysis of several thousand d‐ vs. l‐NaClO3 crystals. Remarkably, instead of an expected nearly 50/50 coin‐tossing situation for the d/l crystal frequency, in most of our experiments a statistically significant bias in favor of d‐ over l‐NaClO3 crystals was found. The experiments also showed that the NaClO3 system was relatively insensitive regarding the intentional addition of a variety of optically active agents. Only in some cases, the persisting d‐bias observed in the unseeded experiments slightly increased upon the presence of such additives. Nevertheless, experiments in plastic petri dishes or in presence of fungal spores were able to reverse this bias. A literature survey shows that mainly d‐directed non‐stochastic behavior in the NaClO3 system has been previously observed in other laboratory settings and by the application of different crystallization techniques. So far, the kind of chiral influence that could be at the origin of the observed bias remains unknown. After the examination of several possible chiral influences of physical, chemical and biological origin, we carefully consider the presence of bio‐contaminants as most likely for the cause of this effect.
Temporal trends in prevalence and outcomes of atrial fibrillation in patients undergoing percutaneous coronary intervention
Authors: Morita Yusuke , Hamaguchi Toka , Yamaji Yuhei , Hayashi Hideyuki , Nakane Eisaku , Haruna Yoshisumi , Haruna Tetsuya , Hanyu Michiya , Inoko Moriaki
Published: November 2019

Background

Atrial fibrillation (AF) is the most common arrhythmia in patients undergoing percutaneous coronary intervention (PCI).

Hypothesis

Large administrative data may provide further insight into temporal trends in the prevalence and burden of AF in patients who underwent PCI.

Methods

Using the National Inpatient Sample database in the U.S., AF patients ≥18 years who underwent PCI between 2005 and 2014 and were identified by the International Classification of Diseases, ninth revision, Clinical Modification, were examined. In‐hospital mortality, morbidity, resource use, and medical costs were evaluated in crude and propensity‐matched analyses.

Results

Among an estimated 6 272 232 hospitalizations, of patients undergoing PCI, AF prevalence was 9.9% and steadily increased from 8.6% to 12.0% between 2005 and 2014 (P < .001); there was also a greater proportion of comorbidities. There was a marked increase in AF prevalence among those aged ≥65 years and those undergoing elective PCIs. AF was independently associated with higher in‐hospital mortality and higher rates of transient ischaemic attack/stroke, bleeding complications, and non‐home discharge. Excessive in‐hospital mortality, stroke rate, gastrointestinal bleeding, blood transfusion, length of stay, and costs among AF hospitalizations were consistently observed throughout the study period.

Conclusion

AF becomes more prevalent in patients undergoing PCI, possibly due to a higher comorbidity, particularly in elderly patients with non‐acute indications. Less favorable trends in mortality, bleeding, and stroke among AF patients who underwent PCI were consistent over time. Continuous efforts are needed to improve outcomes and manage strategies for AF patients undergoing PCI.
The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine
Authors: Nafziger Anne N. , Arscott Kelly A. , Cochrane Kristina , Skobieranda Franck , Burt David A. , Fossler Michael J.
Published: November 2019

Oliceridine is a G protein–biased ligand at the μ‐opioid receptor in development for treatment of moderate to severe acute pain. A phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of oliceridine 0.5 mg intravenous (IV) in subjects with end‐stage renal disease (ESRD, n = 9) versus 1 mg in healthy controls (n = 8). A second phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of a 0.5‐mg IV dose in hepatic impairment (mild, n = 10; moderate, n = 10; severe, n = 6) versus 1 mg in healthy controls (n = 8). The controls were sex and age (±10 years) matched. In ESRD versus healthy subjects, no difference in clearance was observed between ESRD patients and subjects with normal renal function. Oliceridine clearance and AUC were not affected by hepatic impairment. Half‐life (hours; GM [%CV]) increased in subjects with moderate (4.3 [44.1]) and severe (5.8 [41.2]) impairment versus mild impairment (2.6 [20.0]) and healthy subjects (2.1 [11.3]). Volume of distribution was increased with the degree of hepatic impairment. All adverse events were mild and generally consistent with the known safety profile of oliceridine. No dose adjustment is needed in patients with renal impairment or in patients with mild or moderate hepatic impairment. Initial dose reduction should be considered in severe hepatic impairment, and patients may require fewer doses of oliceridine due to the longer half‐life observed in these patients.
Safety, Pharmacokinetics, and Mosquito‐Lethal Effects of Ivermectin in Combination With Dihydroartemisinin‐Piperaquine and Primaquine in Healthy Adult Thai Subjects
Authors: Kobylinski Kevin C. , Jittamala Podjanee , Hanboonkunupakarn Borimas , Pukrittayakamee Sasithon , Pantuwatana Kanchana , Phasomkusolsil Siriporn , Davidson Silas A. , Winterberg Markus , Hoglund Richard M. , Mukaka Mavuto , van der Pluijm Rob W. , Dondorp Arjen , Day Nicholas P.J. , White Nicholas J. , Tarning Joel
Published: November 2019

Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito‐lethal effects of combinations of ivermectin, dihydroartemisinin‐piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin‐piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito‐lethal effect across all subjects. Exposure to piperaquine was also increased when coadministered with ivermectin, but electrocardiograph QT‐interval prolongation was not increased. One subject had transiently impaired liver function. Ivermectin mosquito‐lethal effect was greater than predicted previously against the major Southeast Asian malaria vectors. Both Anopheles dirus and Anopheles minimus mosquito mortality was increased substantially (20‐fold and 35‐fold increase, respectively) when feeding on volunteer blood after ivermectin administration compared with in vitro ivermectin‐spiked blood. This suggests the presence of ivermectin metabolites that impart mosquito‐lethal effects. Further studies of this combined approach to accelerate malaria elimination are warranted.
Leukemia‐associated immunophenotypes subdivided in “categories of specificity” improve the sensitivity of minimal residual disease in predicting relapse in acute myeloid leukemia
Authors: Rossi Giovanni , Giambra Vincenzo , Minervini Maria M. , De Waure Chiara , Mancinelli Silvia , Ciavarella Michele , Sinisi Nicola P. , Scalzulli Potito R. , Carella Angelo M. , Cascavilla Nicola
Published: November 2019

Background

The assessment of minimal residual disease (MRD) by flow cytometry (FC) has a prognostic impact in acute myeloid leukemia (AML), despite the low sensitivity in predicting relapse. Nonetheless, the role of leukemic‐associated immunophenotypes (LAIPs)‐related specificity on the sensitivity of MRD has not been clarified yet. In this respect, we accomplished this study.

Methods

LAIP‐frequencies of bone marrow samples from healthy donors and patients after treatment were quantified and subdivided in “categories of specificity” named as: “strong,” “good,” and “weak.” At the following, the diagnostic performance of MRD was investigated in terms of sensitivity, specificity, predictive values, likelihood ratio (LR).

Results

“Strong” LAIPs were identified by CD7, CD2, CD4, and CD56 markers while “weak” LAIPs, independently of coexpressed markers, were mainly observed in CD33+ cells. MRD identified patients with significantly low DFS and OS but showed a low sensitivity in predicting relapse. Interestingly, majority of recurrences was noticed in patients with two LAIPs and lacking of “strong” LAIPs or only with one “good” LAIP. Thus, only patients showing one “strong” or two “good” LAIPs were considered suitable for MRD monitoring and selected to be further investigated. In this subset, positive MRD predicted a poor prognosis. Moreover, a higher sensitivity, negative predictive value (NPV) and LR‐ were observed after comparison with the previous series.

Conclusions

These data highlight the relevant role of LAIP classification in “categories of specificity” in improving the sensitivity of MRD as assessed by FC.
Novel 5‐(1‐aryl‐1H‐pyrazol‐3‐yl)‐1H‐tetrazoles as glycogen phosphorylase inhibitors: An in vivo antihyperglycemic activity study
Authors: Kattimani Pramod P. , Somagond Shilpa M. , Bayannavar Praveen K. , Kamble Ravindra R. , Bijjaragi Subhas C. , Hunnur Raveendra K. , Joshi Shrinivas D.
Published: November 2019

In this study, we report the ring transformation of 3‐arylsydnone into 1‐aryl‐1H‐pyrazole‐3‐carbonitriles via [3 + 2] cycloaddition with acrylonitrile. 1‐Aryl‐1H‐pyrazole‐3‐carbonitrile underwent [2 + 3] cycloaddition with sodium azide to afford 5‐(1‐aryl‐1H‐pyrazol‐3‐yl)‐1H‐tetrazoles which were further subjected to N‐alkylation with aryl/heteroaryl alkyl halides to afford 1,5‐ and 2,5‐disubstituted tetrazoles. Furthermore, the title compounds were screened for in vivo antihyperglycemic activity using albino Wistar rats of either sex. Compounds 4a, 6b, 7a, 7b, 8b, and 9b showed maximum fall in the blood glucose levels in streptozotocin‐induced diabetic rats after 5–7 days of administration. In support of antidiabetic activity, we also performed the experimental in vivo studies, namely, effect of compounds on enzymes (serum glutamic oxaloacetic transaminase, serum glutamic‐pyruvic transaminase, creatinine, urea, and total protein), antihyperlipidemic, and histopathology. Moreover, the molecular docking study has been performed for potent molecules among the series with glycogen phosphorylase as target enzyme, and this study corroborated the experimental in vivo results.
Crystal Chemistry and SAXS Studies of an Octahedral Polyoxoarsenotungstate Nanocluster Encapsulating Four Unprecedented Thorium Arsenate Fragments ({Th3As2On} – n = 25 or 26)
Authors: Dufaye Maxime , Duval Sylvain , Stoclet Grégory , Loiseau Thierry
Published: November 2019

Invited for the cover of this issue is Sylvain Duval, Associate Professor in the group of Thierry Loiseau from Université de Lille, Villeneuve d'Ascq, France. The cover image shows the behavior of a thorium‐containing polyoxometalate upon dissolution in water, monitored by SAXS analysis.
Simultaneous mitigation of 4(5)‐methylimidazole, acrylamide, and 5‐hydroxymethylfurfural in ammonia biscuits by supplementing with food hydrocolloids
Authors: Mousa Rasha M. A.
Published: November 2019

In the current work, methodological approach for the incorporation of food hydrocolloids gum Arabic (GA), pectin, and carboxymethylcellulose (CMC) in biscuit dough was firstly investigated to mitigate simultaneously the formation of 4(5)‐methylimidazole (4(5)‐MI), acrylamide (AA), and 5‐hydroxymethylfurfural (5‐HMF) in ammonia biscuits. Results revealed that the percent inhibition of 4(5)‐MI was ranged from 50.5% to 89.9% by increasing the GA amount from 0.01 g to 0.05 g, respectively. Furthermore, the use of 0.05 g GA reduced significantly AA content up to 58.6% compared to the control biscuits. Moreover, the highest inhibition of 5‐HMF with 74% depression was achieved by 0.05 g GA. Reasons could be referred to the formation of GA layer on the surface of biscuits. This was confirmed by scanning electron microscope and water loss analysis. Additionally, browning intensity and sensory analysis showed that the supplementation with GA had preserved the quality and consumers’ overall acceptability of ammonia biscuits.
Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72
Authors: Bocchetta Martina , Iglesias Juan E. , Neason Mollie , Cash David M. , Warren Jason D. , Rohrer Jonathan D.
Published: November 2019

Thalamic atrophy is a common feature across all forms of FTD but little is known about specific nuclei involvement. We aimed to investigate in vivo atrophy of the thalamic nuclei across the FTD spectrum. A cohort of 402 FTD patients (age: mean(SD) 64.3(8.2) years; disease duration: 4.8(2.8) years) was compared with 104 age‐matched controls (age: 62.5(10.4) years), using an automated segmentation of T1‐weighted MRIs to extract volumes of 14 thalamic nuclei. Stratification was performed by clinical diagnosis (180 behavioural variant FTD (bvFTD), 85 semantic variant primary progressive aphasia (svPPA), 114 nonfluent variant PPA (nfvPPA), 15 PPA not otherwise specified (PPA‐NOS), and 8 with associated motor neurone disease (FTD‐MND), genetic diagnosis (27 MAPT, 28 C9orf72, 18 GRN), and pathological confirmation (37 tauopathy, 38 TDP‐43opathy, 4 FUSopathy). The mediodorsal nucleus (MD) was the only nucleus affected in all FTD subgroups (16–33% smaller than controls). The laterodorsal nucleus was also particularly affected in genetic cases (28–38%), TDP‐43 type A (47%), tau‐CBD (44%), and FTD‐MND (53%). The pulvinar was affected only in the C9orf72 group (16%). Both the lateral and medial geniculate nuclei were also affected in the genetic cases (10–20%), particularly the LGN in C9orf72 expansion carriers. Use of individual thalamic nuclei volumes provided higher accuracy in discriminating between FTD groups than the whole thalamic volume. The MD is the only structure affected across all FTD groups. Differential involvement of the thalamic nuclei among FTD forms is seen, with a unique pattern of atrophy in the pulvinar in C9orf72 expansion carriers.
Stathmin 1 Induces Murine Hepatocyte Proliferation and Increased Liver Mass
Authors: Zhao Enpeng , Shen Yang , Amir Muhammad , Farris Alton B. , Czaja Mark J.
Published: November 2019

The endogenous cellular signals that initiate the transition of hepatocytes from quiescence to proliferation remain unclear. The protein stathmin 1 (STMN1) is highly expressed in dividing cells, including hepatocytes, and functions to promote cell mitosis through physical interactions with tubulin and microtubules that regulate mitotic spindle formation. The recent finding that STMN1 mediates the resistance of cultured hepatocytes to oxidant stress led to an examination of the expression and function of this protein in the liver in vivo. STMN1 messenger RNA (mRNA) and protein were essentially undetectable in normal mouse liver but increased markedly in response to oxidant injury from carbon tetrachloride. Similarly, levels of STMN1 mRNA and protein were increased in human livers from patients with acute fulminant hepatic failure. To determine STMN1 function in the liver in vivo, mice were infected with a control or Stmn1‐expressing adenovirus. Stmn1 expression induced spontaneous liver enlargement with a doubling of the liver to body weight ratio. The increase in liver mass resulted, in part, from hepatocellular hypertrophy but mainly from an induction of hepatocyte proliferation. STMN1 expression led to marked increases in the numbers of 5‐bromo‐2′‐deoxyuridine‐positive and mitotic hepatocytes and hepatic nuclear levels of cyclins and cyclin‐dependent kinases. STMN1‐induced hepatocyte proliferation was followed by an apoptotic response and a return of the liver to its normal mass. Conclusion: STMN1 promotes entry of quiescent hepatocytes into the cell cycle. STMN1 expression by itself in the absence of any reduction in liver mass is sufficient to stimulate a hepatic proliferative response that significantly increases liver mass.
Demographic transition and economic growth: Evidence from China and United States
Authors: Ye Liping , Zhang Xinping , Geng Jiangbo
Published: November 2019

In the context of todays ageing population, this paper uses the connectedness network model proposed by Diebold and Yilmaz in 2014 to analyse the directionality and degree of interaction between the population ageing index, life expectancy, per capita gross domestic product, and per capita health expenditure from a systematic perspective for China; then, these results from China are compared with the United States. A number of new findings can be identified, as follows: (1) for China and the United States, economic growth may promote the growth of health expenditure and increased life expectancy may cause an increase in the ageing population; (2) China's population age structure has already led to some constraints on economic growth, whereas the United StatesUS's population age structure has had a weak impact on its economic growth; and (3) the ageing population structure for China has a net impact on per capita health expenditure, whereas no such net directional impact was found in the United States. These findings support the idea that policy synergies should be strengthened in the economic, social, and health fields in order to promote both the quality of life of the ageing population and the sustainable development of the economy.
Characterization of the conversion of bone cement and borate bioactive glass composites
Authors: Cole Kimberly A. , Funk Grahmm A. , Rahaman Mohamed N. , McIff Terence E.
Published: November 2019

Borate bioactive glass 13‐93B3 converts into an osteoconductive hydroxyapatite‐like material in a liquid medium. In this study, 13‐93B3 was incorporated into a commercial PMMA (poly(methyl methacrylate)) bone cement, and the conversion of the glass into a precipitate in solution was investigated with scanning electron microscopy, energy dispersive X‐ray spectroscopy, Fourier transform infrared (spectroscopy)—attenuated total reflection, and micro‐Raman spectroscopy. Glass particles of 5, 33, and 100 μm diameter were each mixed with the PMMA cement to create 20, 30, and 40% glass‐loaded composites. Precipitate formation was found to be a calcium‐deficient apatite partially substituted with magnesium ions that resembles native bone material and would ideally encourage bone growth better than stoichiometric hydroxyapatite. Composites of bone cement and 13‐93B3 show promise as a means of encouraging bone attachment to the surface of the bone cement.
SNHG16 as the miRNA let‐7b‐5p sponge facilitates the G2/M and epithelial‐mesenchymal transition by regulating CDC25B and HMGA2 expression in hepatocellular carcinoma
Authors: Li Shengguang , Peng Fujun , Ning Yichong , Jiang Peng , Peng Jian , Ding Xiaofeng , Zhang Jian , Jiang Taijiao , Xiang Shuanglin
Published: November 2019

Long noncoding RNAs (lncRNAs) play crucial roles in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of small nucleolar RNA host gene 16 (SNHG16) for regulating the cell cycle and epithelial to mesenchymal transition (EMT) remain elusive. In this study, SNHG16 expression profiles of HCC tissues or cell lines were compared with those of normal tissues or hepatocyte cell line. The effect of SNHG16 knockdown in HCC cell lines was investigated by using in vitro loss‐of‐function experiments and in vivo nude mouse experiments. The potential molecular regulatory mechanism of SNHG16 in HCC progression was investigated by using mechanistic experiments and rescue assays. The results revealed that SNHG16 was highly expressed in HCC tissues and cell lines, which predicted poor prognosis of HCC patients. On one hand, the downregulation of SNHG16 induced G2/M cell cycle arrest, inducing cell apoptosis and suppression of cell proliferation. On the other hand, it inhibited cell metastasis and EMT progression demonstrated by in vitro loss‐of‐function cell experiments. Besides, knockdown of SNHG16 increased the sensitivity of HCC cells to cisplatin. For the detailed mechanism, SNHG16 was demonstrated to act as a let‐7b‐5p sponge in HCC. SNHG16 facilitated the G2/M cell cycle transition by directly acting on the let‐7b‐5p/CDC25B/CDK1 axis, and promoted cell metastasis and EMT progression by regulating the let‐7b‐5p/HMGA2 axis in HCC. In addition, the mechanism of SNHG16 for regulating HCC cell proliferation and metastasis was further confirmed in vivo by mouse experiments. Furthermore, these results can provide new insights into HCC treatment and its molecular pathogenesis, which may enlighten the further research of the molecular pathogenesis of HCC.
In vitro knock‐out of miR‐155 suppresses leukemic and HCV virus loads in pediatric HCV‐4–associated acute lymphoid leukemia: A promising target therapy
Authors: Hassan Safaa S. , El‐Khazragy Nashwa , Elshimy Amal A. , Aboelhussein Marwa M. , Saleh Shereen A. , Fadel Sayed , Atia Hend A. , Matbouly Safa , Tamer Natalie
Published: November 2019

Hepatitis C virus (HCV) infection is a major public health problem, having a high prevalence in Egypt. Leukemia and lymphoma have been associated with HCV infection. MicroRNA‐155 (miR‐155) has been reported to play a regulatory role in cancer, inflammation, and immune response to infection. The expression level of miR‐155 in HCV viremic patients is controversial; although high miR‐155 levels were demonstrated in HCV genotypes 1,2, and 3, low levels of miR‐155 were detected in Egyptian patients with HCV genotype 4. Several studies have investigated the correlation between the levels of miRNA‐155 and the replication of HCV, others have evaluated miRNA‐155 as a prognostic biomarker in different types of cancer. No studies have investigated the impact of miRNA‐155 knockdown on HCV pediatric patients associated with childhood acute lymphoblastic leukemia (ALL). We knocked‐out the miR_155a in cultured polymorphonuclear cells (PBMCs) obtained from 60 children with ALL; 30 were associated with HCV‐4 infection and 30 were HCV negative. The miR_155a, HCV viral load, and cell proliferation werre assessed in treated and untreated cells using TaqMan assay quantitative polymerase chain reaction. We found that miRNA‐155 was significantly upregulated by seven folds in the HCV‐4 associated ALL group; while being linked to high HCV viral load and leukemic burden, miR_155a knock‐out can improve the disease outcome. We conclude that miR‐155 is a critical miRNA that is considered a therapeutic target in pediatric HCV leukemic patients.
Vibration of osteoblastic cells using a novel motion‐control platform does not acutely alter cytosolic calcium, but desensitizes subsequent responses to extracellular ATP
Authors: Lorusso Daniel , Nikolov Hristo N. , Holdsworth David W. , Dixon S. Jeffrey
Published: November 2019

Low‐magnitude high‐frequency mechanical vibration induces biological responses in many tissues. Like many cell types, osteoblasts respond rapidly to certain forms of mechanostimulation, such as fluid shear, with transient elevation in the concentration of cytosolic free calcium ([Ca2+]i). However, it is not known whether vibration of osteoblastic cells also induces acute elevation in [Ca2+]i. To address this question, we built a platform for vibrating live cells that is compatible with microscopy and microspectrofluorometry, enabling us to observe immediate responses of cells to low‐magnitude high‐frequency vibrations. The horizontal vibration system was mounted on an inverted microscope, and its mechanical performance was evaluated using optical tracking and accelerometry. The platform was driven by a sinusoidal signal at 20–500 Hz, producing peak accelerations from 0.1 to 1 g. Accelerometer‐derived displacements matched those observed optically within 10%. We then used this system to investigate the effect of acceleration on [Ca2+]iin rodent osteoblastic cells. Cells were loaded with fura‐2, and [Ca2+]iwas monitored using microspectrofluorometry and fluorescence ratio imaging. No acute changes in [Ca2+]ior cell morphology were detected in response to vibration over the range of frequencies and accelerations studied. However, vibration did attenuate Ca2+transients generated subsequently by extracellular ATP, which activates P2 purinoceptors and has been implicated in mechanical signaling in bone. In summary, we developed and validated a motion‐control system capable of precisely delivering vibrations to live cells during real‐time microscopy. Vibration did not elicit acute elevation of [Ca2+]i, but did desensitize responses to later stimulation with ATP.
MicroRNA‐497 functions as an inflammatory suppressor via targeting DDX3Y and modulating toll‐like receptor 4/NF‐κB in cigarette smoke extract‐stimulated human bronchial epithelial cells
Authors: Jia Rong , Zhao Xiao‐Fei
Published: November 2019

Background

We aimed to investigate the biological effect of miR‐497 in cigarette smoke extract (CSE)‐damaged human bronchial epithelial (HBE) cells and the underlying molecular mechanism.

Methods

MiR‐497 mimic was transfected into HBE cells to up‐regulate miR‐497 expression. Cigarette smoke extract (CSE, 20 μg/mL) was utilized to treat HBE cells to form the injury model. Cell proliferation and apoptosis were detected by CCK8 and flow cytometry assays. DDX3Y mRNA expression was determined by a quantitative reverse transcriptase‐polymerase chain reaction. The interaction between miR‐497 and DDX3Y was verified by a luciferase reporter assay. Protein expression levels were tested by western blotting.

Results

CSE treatment decreased miR‐497 level in HBE cells. CSE exposure restrained cell proliferation, promoted cell apoptosis and enhanced the relative expression of TLR4 and p‐NF‐κB p65. DDX3Y was predicted as a target of miR‐497. The mRNA and protein expression of DDX3Y was negatively modulated by miR‐497 in CSE‐injured HBE cells. Up‐regulation of miR‐497 by miR‐497 mimic increased cell proliferation and reduced cell apoptosis in CSE‐treated HBE cells, which were rescued by DDX3Y high expression in CSE‐treated HBE cells. Consistently, Bcl‐2 protein level was heightened, whereas Bax and actived caspase‐3/9 protein levels were decreased by miR‐497 mimic in CSE‐stimulated HBE cells, which was reversed by DDX3Y over‐expression in CSE‐stimulated HBE cells. The relative expression of TLR4 and p‐NF‐κB p65 was decreased by miR‐497 mimic, whereas they were rescued by DDX3Y over‐expression in CSE‐damaged HBE cells.

Conclusions

The results of the present study demonstrate that up‐regulation of miR‐497 exhibits a protective effect on CSE‐damaged HBE cells, which might be achieved by targeting DDX3Y and regulating the TLR4/NF‐κB pathway.
In vivo uterine local gene delivery system using TAT‐displaying bionanocapsules
Authors: Koizumi Kaori , Nakamura Hitomi , Iijima Masumi , Matsuzaki Takashi , Somiya Masaharu , Kumasawa Keiichi , Kimura Tadashi , Kuroda Shun'ichi
Published: November 2019

Background

The uterus is an organ that is directly accessible via the transvaginal route, whereas the drug delivery system and the gene delivery system (GDS) for the uterus are very limited, even in animal models. In the present study, we optimized a bionanocapsule (BNC) comprising a hepatitis B virus envelope L‐protein particle, for which a structurally similar particle has been used as an immunogen of a conventional HB vaccine worldwide for more than 30 years, as a local uterine GDS using a mouse model.

Methods

To display various antibodies for re‐targeting to different cells other than hepatic cells, the pre‐S1 region of BNC was replaced with a tandem form of the protein A‐derived immunoglobulin G Fc‐interacting region (Z domain, ZZ‐BNC). To induce strong cell adhesion after local administration into the uterine cavity, ZZ‐BNC was modified with a transactivator of transcription (TAT) peptide.

Results

Gene transfer using TAT‐modified ZZ‐BNC is approximately 5000‐ or 18‐fold more efficient than the introduction of the same dose of naked DNAs or the use of the cationic liposomes, respectively. TAT‐modified ZZ‐BNC was rapidly eliminated from the uterus and had no effect on the pregnancy rate, litter size or fetal growth.

Conclusions

TAT‐modified ZZ‐BNC could be a useful GDS for uterine endometrial therapy via local uterine injection.
An improved preparation of [18F]AV‐45 by simplified solid‐phase extraction purification
Authors: Zhang Lifang , Zhang Aili , Yao Xinyue , Zhang Yan , Liu Futao , Hong Haiyan , Zha Zhihao , Liu Yajing , Wu Zehui , Qiao Jinping , Zhu Lin , Kung Hank F.
Published: November 2019

Amyvid (florbetapir f18, [18F]AV‐45, [18F]5) was the first FDA‐approved positron emission tomography imaging agent targeting β‐amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [18F]AV‐45 ([18F]5) preparation by using solid‐phase extraction (SPE) purification. [18F]AV‐45 ([18F]5) was synthesized by direct nucleophilic radiofluorination of O‐tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N‐Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [18F]AV‐45 ([18F]5) on the cartridge. The final dose was eluted by ethanol. [18F]AV‐45 ([18F]5) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 μg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 μg/dose). In summary, [18F]AV‐45 ([18F]5) was produced efficiently and reproducibly using a cartridge‐based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [18F]FDG.
High‐resolution ion mobility spectrometry‐mass spectrometry of isomeric/isobaric ribonucleotide variants
Authors: Kenderdine Thomas , Nemati Reza , Baker Andrew , Palmer Martin , Ujma Jakub , FitzGibbon Molly , Deng Limin , Royzen Maksim , Langridge James , Fabris Daniele
Published: November 2019

In this report, we explored the benefits of cyclic ion mobility (cIM) mass spectrometry in the analysis of isomeric post‐transcriptional modifications of RNA. Standard methyl‐cytidine samples were initially utilized to test the ability to correctly distinguish different structures sharing the same elemental composition and thus molecular mass. Analyzed individually, the analytes displayed characteristic arrival times (tD) determined by the different positions of the modifying methyl groups onto the common cytidine scaffold. Analyzed in mixture, the widths of the respective signals resulted in significant overlap that initially prevented their resolution on the tD scale. The separation of the four isomers was achieved by increasing the number of passes through the cIM device, which enabled to fully differentiate the characteristic ion mobility behaviors associated with very subtle structural variations. The placement of the cIM device between the mass‐selective quadrupole and the time‐of‐flight analyzer allowed us to perform gas‐phase activation of each of these ion populations, which had been first isolated according to a common mass‐to‐charge ratio and then separated on the basis of different ion mobility behaviors. The observed fragmentation patterns confirmed the structures of the various isomers thus substantiating the benefits of complementing unique tD information with specific fragmentation data to reach more stringent analyte identification. These capabilities were further tested by analyzing natural mono‐nucleotide mixtures obtained by exonuclease digestion of total RNA extracts. In particular, the combination of cIM separation and post‐mobility dissociation allowed us to establish the composition of methyl‐cytidine and methyl‐adenine components present in the entire transcriptome of HeLa cells. For this reason, we expect that this technique will benefit not only epitranscriptomic studies requiring the determination of identity and expression levels of RNA modifications, but also metabolomics investigations involving the analysis of natural extracts that may possibly contain subsets of isomeric/isobaric species.
Prevalence and protective factors of HIV and syphilis infection among men who have sex with men in Northwest China
Authors: Wang Lirong , Santella Anthony J. , Wei Xiaoli , Zhuang Guihua , Li Hengxin , Zhang Hailan , Huang Xiaodan , Zhang Yalan , Zheng Haichao , Zhou Anqin
Published: November 2019

Background

Men who have sex with men (MSM) continue to be disproportionately impacted by human immunodeficiency virus (HIV) and syphilis in China. Little is known about HIV and syphilis infections among MSM in Xi'an, a developing city in Northwest China. A cross‐sectional study with recruitment via snowball sampling was conducted to collect HIV and syphilis infection status and risk factors among MSM in Xi'an between April 2013 to December 2016. Among the 5000 participants, the mean age was 29.0 years (SD 7.7) and the prevalence of HIV, syphilis, and coinfection was 6.5%, 2.2%, and 0.4%, respectively. There was no significant change in HIV prevalence from 2013 to 2016, while the prevalence of syphilis and coinfection showed a downward trend. Multiple logistic regression analyses found that being over 25 years old (OR = 1.647), junior high school/middle school education and below (OR = 3.085), with a sexual role of passive or versatile (OR = 3.300; OR = 2.337), rush poppers use during the last 6 months (OR = 1.660) and syphilis infection (OR = 2.235) were more likely to acquire HIV infection, whereas used condoms in the last episode of anal sex (OR = 0.572) and tested HIV antibody previously (OR = 0.252) were protective factors for HIV infection. HIV prevalence among MSM in Xi'an was stable, whereas the prevalence of syphilis and coinfection showed a downward trend. Interventions to promote HIV and sexually transmitted disease testing and condom use should be strengthened, especially for MSM with low education.
The papillomavirus E5 gene does not affect EGFR transcription and overall survival in cervical cancer
Authors: Basto Diogo Lisbôa , Chaves Cláudia Bessa Pereira , Felix Shayany Pinto , Amaro‐Filho Sérgio Menezes , Vieira Valdimara Corrêa , Martins Luís Felipe Leite , de Carvalho Neile Alves , Almeida Liz Maria , Moreira Miguel Ângelo Martins
Published: November 2019

Introduction

The human papillomavirus (HPV) E5 gene encodes a small and highly hydrophobic oncoprotein that affects immune evasion, cell proliferation, loss of apoptotic capacity and angiogenesis in tumors. E5 shows an affinity for biological membranes and was associated with an increase of epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling through the accumulation of EGFR in cellular membranes. Due to the frequent integration of the HPV genome into the host cell genome, E5 is frequently not transcribed in cervical tumors.

Aim

In this study we looked forward to verifying whether the potential expression of E5 protein in human papillomavirus 16 positive (HPV16+) and human papillomavirus 18 positive (HPV18+) cervical tumors was associated with levels of EGFR and vascular endothelial growth factor A (VEGFA) transcription and with patients overall survival.

Results

Association between the presence of E5 transcripts and viral genome disruption was observed for HPV16+ and HPV18+ tumors. Association was not observed between tumors potentially capable of translating E5 and EGFR or VEGFA transcriptional levels. Similarly, the capability of translating E5 and overall survival in patients with HPV16+ squamous cell carcinoma tumors stage ≥ IB2 were not associated.

Conclusion

The likely presence of E5 transcripts was neither associated to a higher activity of the EGFR‐VEGFA pathway nor to the overall survival of patients with HPV16+ squamous cell carcinoma in stages ≥ IB2.
Evaluation of high‐throughput digital lateral flow immunoassays for the detection of influenza A/B viruses from clinical swab samples
Authors: Yoo Soo J. , Shim Hee S. , Yoon Sumi , Moon Hee‐Won
Published: November 2019

We evaluated the performance of new high‐throughput digital lateral flow immunoassays (LFIAs) detecting influenza antigens and compared them with those of the widely used digital LFIA and the rapid nucleic acid amplification test (NAAT). We tested 199 clinical nasopharyngeal (nasal) swab samples using three LFIA tests (BD Veritor Plus, STANDARD F Influenza A/B FIA, and ichroma TRIAS) and the rapid NAAT (ID NOW Influenza A & B2). Agreements and clinical performances (sensitivity and specificity) were evaluated based on the results of reverse transcriptase‐polymerase chain reaction (RT‐PCR) and verification panel. The agreement of each test with RT‐PCR was moderate to almost perfect. The sensitivity of ID NOW was significantly higher than that of LFIAs (P = .0005, .0044, and .0026 for influenza A and P = .0044, .0026, and .0044 for influenza B, respectively). The specificities were not significantly different between the four tests (P > .05). However, the reference panel suggests that ichroma TRIAS test is more sensitive than the other two LFIA tests. All three LFIA assays performed similarly with no false positives against influenza A. For influenza B, ichroma TRIAS had 2 of 166 false positives whereas there were no false positives for the other two LFIA tests. Influenza antigen digital LFIAs have advantages in terms of the workflow when simultaneous tests are required. Rapid NAAT has higher sensitivity, while new antigen LFIAs are efficient and high‐throughput. It is recommended that users select appropriate methods and algorithms according to the number of specimens and laboratory conditions in each clinical laboratory.