bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast and covariate-adaptive method amplifies detection power in large-scale multiple hypothesis testing
Authors: Zhang Martin J. , Xia Fei , Zou James
Published: July 2019

Multiple hypothesis testing is an essential component of modern data science. In many settings, in addition to thep-value, additional covariates for each hypothesis are available, e.g., functional annotation of variants in genome-wide association studies. Such information is ignored by popular multiple testing approaches such as the Benjamini-Hochberg procedure (BH). Here we introduce , a fast and flexible method that adaptively learns the optimalp-value threshold from covariates to significantly improve detection power. On eQTL analysis of the GTEx data, discovers 32% more associations than BH at the same false discovery rate. We prove that controls false discovery proportion and show that it makes substantially more discoveries while controlling false discovery rate (FDR) in extensive experiments. is computationally efficient and allows multi-dimensional covariates with both numeric and categorical values, making it broadly useful across many applications.
Standard screening methods underreport AAV-mediated transduction and gene editing
Authors: Lang Jonathan F. , Toulmin Sushila A. , Brida Kasey L. , Eisenlohr Laurence C. , Davidson Beverly L.
Published: July 2019

Conventional methods to discern adeno-associated virus (AAV) vector transduction patterns are based on high, stable expression of a reporter gene. As a consequence, conventionally described tropisms omit cell types that undergo transient transduction, or have low but undetectable levels of reporter expression. This creates a blind spot for AAV-based genome editing applications because only minimal transgene expression is required for activity. Here, we use editing-reporter mice to fill this void. Our approach sensitively captures both high and low transgene expression from AAV vectors. Using AAV8 and other serotypes, we demonstrate the superiority of the approach in a side-by-side comparison with traditional methods, demonstrate numerous, previously unknown sites of AAV targeting, and better predict the gene editing footprint after AAV-CRISPR delivery. We anticipate that this system, which captures the full spectrum of transduction patterns from AAV vectors in vivo, will be foundational to current and emerging AAV technologies.
A highly transparent and ultra-stretchable conductor with stable conductivity during large deformation
Authors: Lei Zhouyue , Wu Peiyi
Published: July 2019

Intrinsically stretchable conductors have undergone rapid development in the past few years and a variety of strategies have been established to improve their electro-mechanical properties. However, ranging from electronically to ionically conductive materials, they are usually vulnerable either to large deformation or at high/low temperatures, mainly due to the fact that conductive domains are generally incompatible with neighboring elastic networks. This is a problem that is usually overlooked and remains challenging to address. Here, we introduce synergistic effect between conductive zwitterionic nanochannels and dynamic hydrogen-bonding networks to break the limitations. The conductor is highly transparent (>90% transmittance), ultra-stretchable (>10,000% strain), high-modulus (>2 MPa Young’s modulus), self-healing, and capable of maintaining stable conductivity during large deformation and at different temperatures. Transparent integrated systems are further demonstrated via 3D printing of its precursor and could achieve diverse sensory capabilities towards strain, temperature, humidity, etc., and even recognition of different liquids.
Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone
Authors: Vrahnas Christina , Blank Martha , Dite Toby A. , Tatarczuch Liliana , Ansari Niloufar , Crimeen-Irwin Blessing , Nguyen Huynh , Forwood Mark R. , Hu Yifang , Ikegame Mika , Bambery Keith R. , Petibois Cyril , Mackie Eleanor J. , Tobin Mark J. , Smyth Gordon K. , Oakhill Jonathan S. , Martin T. John , Sims Natalie A.
Published: July 2019

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass.
Time-reversal symmetry breaking type-II Weyl state in YbMnBi2
Authors: Borisenko Sergey , Evtushinsky Daniil , Gibson Quinn , Yaresko Alexander , Koepernik Klaus , Kim Timur , Ali Mazhar , van den Brink Jeroen , Hoesch Moritz , Fedorov Alexander , Haubold Erik , Kushnirenko Yevhen , Soldatov Ivan , Schäfer Rudolf , Cava Robert J.
Published: July 2019

Spectroscopic detection of Dirac and Weyl fermions in real materials is vital for both, promising applications and fundamental bridge between high-energy and condensed-matter physics. While the presence of Dirac and noncentrosymmetric Weyl fermions is well established in many materials, the magnetic Weyl semimetals still escape direct experimental detection. In order to find a time-reversal symmetry breaking Weyl state we design two materials and present here experimental and theoretical evidence of realization of such a state in one of them, YbMnBi2. We model the time-reversal symmetry breaking observed by magnetization and magneto-optical microscopy measurements by canted antiferromagnetism and find a number of Weyl points. Using angle-resolved photoemission, we directly observe two pairs of Weyl points connected by the Fermi arcs. Our results not only provide a fundamental link between the two areas of physics, but also demonstrate the practical way to design novel materials with exotic properties.
Mechanical unfolding of spectrin reveals a super-exponential dependence of unfolding rate on force
Authors: Renn J. P. , Bhattacharyya S. , Bai H. , He C. , Li H. , Oberhauser A. F. , Marko J. F. , Makarov D. E. , Matouschek A.
Published: July 2019

We investigated the mechanical unfolding of single spectrin molecules over a broad range of loading rates and thus unfolding forces by combining magnetic tweezers with atomic force microscopy. We find that the mean unfolding force increases logarithmically with loading rate at low loading rates, but the increase slows at loading rates above 1pN/s. This behavior indicates an unfolding rate that increases exponentially with the applied force at low forces, as expected on the basis of one-dimensional models of protein unfolding. At higher forces, however, the increase of the unfolding rate with the force becomes faster than exponential, which may indicate anti-Hammond behavior where the structures of the folded and transition states become more different as their free energies become more similar. Such behavior is rarely observed and can be explained by either a change in the unfolding pathway or as a reflection of a multidimensional energy landscape of proteins under force.
The language context effect in facial expressions processing and its mandatory characteristic
Authors: Liu Shen , Tan Qun , Han Shangfeng , Li Wanyue , Wang Xiujuan , Gan Yetong , Xu Qiang , Zhang Xiaochu , Zhang Lin
Published: July 2019

Background visual scenes in which faces are perceived provide contextual information for facial expression processing. One type of background information, the language context, has a vital influence on facial expression processing. The current study is aimed to investigate the effect of the language context on facial expression processing by recording event-related potentials (ERPs). Experiment one adopted the facial expression categorization task to investigate the effects of different language contexts on emotional and non-emotional facial processing. Experiment two adopted the task-irrelevant paradigm to investigate whether the language context effect on facial expression processing was mandatory. The results found that (1) the language context affected facial expression processing. Facial expression processing was promoted when the language context was emotionally congruent with faces. Moreover, the language context had an evoking effect on neutral faces. To be detailed, neutral facial expressions were evoked to be judged as positive in the positive language context while as negative in the negative language context. (2) The language context effect still affected facial expression processing in a task-irrelevant paradigm. When the language context was emotionally incongruent with facial expressions, larger N170 and LPP amplitudes were elicited, indicating the inhibition of incongruent emotions. These findings prove that the language context effect on facial expression processing is mandatory.
Parallel Fourier ptychographic microscopy for high-throughput screening with 96 cameras (96 Eyes)
Authors: Chan Antony C. S. , Kim Jinho , Pan An , Xu Han , Nojima Dana , Hale Christopher , Wang Songli , Yang Changhuei
Published: July 2019

We report the implementation of a parallel microscopy system (96 Eyes) that is capable of simultaneous imaging of all wells on a 96-well plate. The optical system consists of 96 microscopy units, where each unit is made out of a four element objective, made through a molded injection process, and a low cost CMOS camera chip. By illuminating the sample with angle varying light and applying Fourier Ptychography, we can improve the effective brightfield imaging numerical aperture of the objectives from 0.23 to 0.3, and extend the depth of field from ±5 μm to ±15 μm. The use of Fourier Ptychography additionally allows us to computationally correct the objectives’ aberrations out of the rendered images, and provides us with the ability to render phase images. The 96 Eyes acquires raw data at a rate of 0.7 frame per second (all wells) and the data are processed with 4 cores of graphical processing units (GPUs; GK210, Nvidia Tesla K80, USA). The system is also capable of fluorescence imaging (excitation = 465 nm, emission = 510 nm) at the native resolution of the objectives. We demonstrate the capability of this system by imaging S1P1-eGFP-Human bone osteosarcoma epithelial (U2OS) cells.
Poor chemical and microbiological quality of the commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non-reproducible clinical outcomes
Authors: Fenclova Marie , Novakova Alena , Viktorova Jitka , Jonatova Petra , Dzuman Zbynek , Ruml Tomas , Kren Vladimir , Hajslova Jana , Vitek Libor , Stranska-Zachariasova Milena
Published: July 2019

Herbal-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum), is often used for the treatment of liver diseases. However, serious concerns exist regarding the efficacy, composition, as well as the safety of these over-the-counter preparations. Therefore, the aim of the present study was to investigate the composition as well as chemical and biological safety of 26 milk thistle-based dietary supplements purchased from both the U.S. and Czech markets between 2016 and 2017. The study was focused on a determination of the composition of active ingredients, as well as analyses of possible contaminants including: mycotoxins, plant alkaloids, and pesticide residues, as well as the microbial purity. High-throughput analyses were performed using advanced U-HPLC-HRMS techniques. Large differences in the silymarin content were observed among individual milk thistle preparations, often in contrast with the information provided by the manufacturers. In addition, substantial inter-batch differences in silymarin content were also demonstrated. In all milk thistle preparations tested, large numbers and high concentrations of mycotoxins and several pesticides, as well as the substantial presence of microbiological contamination were detected, pointing to serious safety issues. In conclusion, our results strongly indicate the need for strict controls of the composition, chemical contaminants, as well as the microbiological purity of commercial milk thistle extracts used for the treatment of liver diseases. Poor definition of these preparations together with contamination by biologically active substances may not only account for the inconsistency of clinical observations, but also be responsible for possible herbal-based dietary supplements-induced liver injury.
Biological motion perception is differentially predicted by Autistic trait domains
Authors: Lee Ka Shu , Chang Dorita H. F.
Published: July 2019

We tested the relationship between biological motion perception and the Autism-Spectrum Quotient. In three experiments, we indexed observers’ performance on a classic left-right discrimination task in which participants were asked to report the facing direction of walkers containing solely structural or kinematics information, a motion discrimination task in which participants were asked to indicate the apparent motion of a (non-biological) random-dot stimulus, and a novel naturalness discrimination task. In the naturalness discrimination task, we systematically manipulated the degree of natural acceleration contained in the stimulus by parametrically morphing between a fully veridical stimulus and one where acceleration was removed. Participants were asked to discriminate the more natural stimulus (i.e., acceleration-containing stimulus) from the constant velocity stimulus. Although we found no reliable associations between overall AQ scores nor subdomain scores with performance on the direction-related tasks, we found a robust association between performance on the biological motion naturalness task and attention switching domain scores. Our findings suggest that understanding the relationship between the Autism Spectrum and perception is a far more intricate problem than previously suggested. While it has been shown that the AQ can be used as a proxy to tap into perceptual endophenotypes in Autism, the eventual diagnostic value of the perceptual task depends on the task’s consideration of biological content and demands.
Decline in maternal death due to obstetric haemorrhage between 2010 and 2017 in Japan
Authors: Hasegawa Junichi , Katsuragi Shinji , Tanaka Hiroaki , Kurasaki Akiko , Nakamura Masamitsu , Murakoshi Takeshi , Nakata Masahiko , Kanayama Naohiro , Sekizawa Akihiko , Isamu Ishiwata , Kinoshita Katsuyuki , Ikeda Tomoaki
Published: July 2019

This descriptive study was based on the maternal death registration system established by the Japan Association of Obstetricians and Gynecologists and the Maternal Death Exploratory Committee (JMDEC). 361 women died during pregnancy or within 42 days after delivery between January 2010 and June 2017 throughout Japan were analysed, in order to investigate the trend in maternal deaths related to obstetric medical practice. Reports of maternal death were consistent, ranging from 45 cases in 2010 to 44 cases in 2017. Among all maternal deaths, the frequency of deaths due to obstetric haemorrhage ranged from 29% (2010) to 7% (2017) (p < 0.001). The causes of obstetric haemorrhage have progressively reduced, especially maternal deaths due to uterine inversion and laceration have not occurred since 2014. The remaining causes of obstetric haemorrhage-related maternal deaths were placenta accreta spectrum, placental abruption, and severe forms of uterine focused amniotic fluid embolism. We believe the activities of the JMDEC including annual recommendations and simulation programs are improving the medical practices of obstetric care providers in Japan, resulting in a reduction of maternal deaths due to obstetric haemorrhage.
Mobile continuous-flow isotope-ratio mass spectrometer system for automated measurements of N2 and N2O fluxes in fertilized cropping systems
Authors: Warner Daniel I. , Scheer Clemens , Friedl Johannes , Rowlings David W. , Brunk Christian , Grace Peter R.
Published: July 2019

The use of synthetic N fertilizers has grown exponentially over the last century, with severe environmental consequences. Most of the reactive N will ultimately be removed by denitrification, but estimates of denitrification are highly uncertain due to methodical constraints of existing methods. Here we present a novel, mobile isotope ratio mass spectrometer system (Field-IRMS) for in-situ quantification of N2 and N2O fluxes from fertilized cropping systems. The system was tested in a sugarcane field continuously monitoring N2 and N2O fluxes for 7 days following fertilization using a fully automated measuring cycle. The detection limit of the Field-IRMS proved to be highly sensitive for N2 (54 g ha−1 day−1) and N2O (0.25 g ha−1 day−1) emissions. The main product of denitrification was N2 with total denitrification losses of up to 1.3 kg N ha−1 day−1. These losses demonstrate sugarcane systems in Australia are a hotspot for denitrification where high emissions of N2O and N2 can be expected. The new Field-IRMS allows for the direct and highly sensitive detection of N2 and N2O fluxes in real time at a high temporal resolution, which will help to improve our quantitative understanding of denitrification in fertilized cropping systems.
Unraveling the role of quorum sensing-dependent metabolic homeostasis of the activated methyl cycle in a cooperative population of Burkholderia glumae
Authors: Kang Yongsung , Kim Hongsup , Goo Eunhye , Jeong Hyesung , An Jae Hyung , Hwang Ingyu
Published: July 2019

The activated methyl cycle (AMC) is responsible for the generation of S-adenosylmethionine (SAM), which is a substrate of N-acylhomoserine lactone (AHL) synthases. However, it is unknown whether AHL-mediated quorum sensing (QS) plays a role in the metabolic flux of the AMC to ensure cell density-dependent biosynthesis of AHL in cooperative populations. Here we show that QS controls metabolic homeostasis of the AMC critical for AHL biosynthesis and cellular methylation in Burkholderia glumae, the causal agent of rice panicle blight. Activation of genes encoding SAM-dependent methyltransferases, S-adenosylhomocysteine (SAH) hydrolase, and methionine synthases involved in the AMC by QS is essential for maintaining the optimal concentrations of methionine, SAM, and SAH required for bacterial cooperativity as cell density increases. Thus, the absence of QS perturbed metabolic homeostasis of the AMC and caused pleiotropic phenotypes in B. glumae. A null mutation in the SAH hydrolase gene negatively affected AHL and ATP biosynthesis and the activity of SAM-dependent methyltransferases including ToxA, which is responsible for the biosynthesis of a key virulence factor toxoflavin in B. glumae. These results indicate that QS controls metabolic flux of the AMC to secure the biosynthesis of AHL and cellular methylation in a cooperative population.
Steroids originating from bacterial bile acid degradation affect Caenorhabditis elegans and indicate potential risks for the fauna of manured soils
Authors: Mendelski M. N. , Dölling R. , Feller F. M. , Hoffmann D. , Ramos Fangmeier L. , Ludwig K. C. , Yücel O. , Mährlein A. , Paul R. J. , Philipp B.
Published: July 2019

Bile acids are steroid compounds from the digestive tracts of vertebrates that enter agricultural environments in unusual high amounts with manure. Bacteria degrading bile acids can readily be isolated from soils and waters including agricultural areas. Under laboratory conditions, these bacteria transiently release steroid compounds as degradation intermediates into the environment. These compounds include androstadienediones (ADDs), which are C19-steroids with potential hormonal effects. Experiments with Caenorhabditis elegans showed that ADDs derived from bacterial bile acid degradation had effects on its tactile response, reproduction rate, and developmental speed. Additional experiments with a deletion mutant as well as transcriptomic analyses indicated that these effects might be conveyed by the putative testosterone receptor NHR-69. Soil microcosms showed that the natural microflora of agricultural soil is readily induced for bile acid degradation accompanied by the transient release of steroid intermediates. Establishment of a model system with a Pseudomonas strain and C. elegans in sand microcosms indicated transient release of ADDs during the course of bile acid degradation and negative effects on the reproduction rate of the nematode. This proof-of-principle study points at bacterial degradation of manure-derived bile acids as a potential and so-far overlooked risk for invertebrates in agricultural soils.
Interaction of PIAS1 with PRRS virus nucleocapsid protein mediates NF-κB activation and triggers proinflammatory mediators during viral infection
Authors: Ke Hanzhong , Lee Sera , Kim Jineui , Liu Hsiao-Ching , Yoo Dongwan
Published: July 2019

Porcine reproductive and respiratory syndrome virus (PRRSV) activates NF-κB during infection. We examined the ability of all 22 PRRSV genes for NF-κB regulation and determined the nucleocapsid (N) protein as the NF-κB activator. Protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1) (PIAS1) was identified as a cellular protein binding to N. PIAS1 is known to bind to p65 (RelA) in the nucleus and blocks its DNA binding, thus functions as a repressor of NF-κB. Binding of N to PIAS1 released p65 for NF-κB activation. The N-terminal half of PIAS1 was mapped as the N-binding domain, and this region overlapped its p65-binding domain. For N, the region between 37 and 72 aa was identified as the binding domain to PIAS1, and this domain alone was able to activate NF-κB. A nuclear localization signal (NLS) knock-out mutant N did not activate NF-κB, and this is mostly likely due to the lack of its interaction with PIAS1 in the nucleus, demonstrating the positive correlation between the binding of N to PIAS1 and the NF-κB activation. Our study reveals a role of N in the nucleus for NF-κB activation and proinflammatory cytokine production during infection.
Individual Differences in Response to Ambiguous Stimuli in a Modified Go/No-Go Paradigm are Associated with Personality in Family Dogs
Authors: Bunford Nóra , Csibra Barbara , Gácsi Márta
Published: July 2019

Cognitive biases, often used as indices of affective and emotional states, are associated with individual differences in personality in humans and have been observed in nonhuman animals, including dogs. Although dogs have complementary advantages over traditional animal models of human cognition, little is known about the relationship between dogs’ cognitive bias and personality. Here, we examined in 29 family dogs (representing 14 breeds and 12 mutts;Mage = 4.59 years,SD = 2.90), the association between naturally occurring – as opposed to experimentally induced – cognitive bias, indexed via active choice behavior in a Go/No-Go (GNG) paradigm reflecting positive/negative expectations about ambiguous stimuli, and owner-rated personality. In a subsample we additionally assessed whether prior inhibition, personality, and inattention (IA)/hyperactivity/impulsivity (H/I) results could be replicated in a modified paradigm. We also explored whether expanding the response time-window would increase GNG errors and whether dogs exhibited differences in their behavioral approach to uncertainty. Findings indicated dogs with higher conscientiousness and extraversion scores were more likely to exhibit a “go” response to ambiguous stimuli. Replicability across prior and current results was generally established, e.g., as previously, IA did not predict GNG performance but extraversion did, whereas H/I predicted different indices of GNG performance. Increased response time-window did not result in differential performance, except for less commission errors. No differences in behavioral response strategy to trained “no-go” and to ambiguous stimuli were apparent. Results evince the dog is a promising animal model of the association between an optimistic cognitive bias and personality.
Development of social learning and play in BaYaka hunter-gatherers of Congo
Authors: Salali Gul Deniz , Chaudhary Nikhil , Bouer Jairo , Thompson James , Vinicius Lucio , Migliano Andrea Bamberg
Published: July 2019

High-fidelity transmission of information through imitation and teaching has been proposed as necessary for cumulative cultural evolution. Yet, it is unclear when and for which knowledge domains children employ different social learning processes. This paper explores the development of social learning processes and play in BaYaka hunter-gatherer children by analysing video recordings and time budgets of children from early infancy to adolescence. From infancy to early childhood, hunter-gatherer children learn mainly by imitating and observing others’ activities. From early childhood, learning occurs mainly in playgroups and through practice. Throughout childhood boys engage in play more often than girls whereas girls start foraging wild plants from early childhood and spend more time in domestic activities and childcare. Sex differences in play reflect the emergence of sexual division of labour and the play-work transition occurring earlier for girls. Consistent with theoretical models, teaching occurs for skills/knowledge that cannot be transmitted with high fidelity through other social learning processes such as the acquisition of abstract information e.g. social norms. Whereas, observational and imitative learning occur for the transmission of visually transparent skills such as tool use, foraging, and cooking. These results suggest that coevolutionary relationships between human sociality, language and teaching have likely been fundamental in the emergence of human cumulative culture.
Radiosensitizing effect of curcumin-loaded lipid nanoparticles in breast cancer cells
Authors: Minafra Luigi , Porcino Nunziatina , Bravatà Valentina , Gaglio Daniela , Bonanomi Marcella , Amore Erika , Cammarata Francesco Paolo , Russo Giorgio , Militello Carmelo , Savoca Gaetano , Baglio Margherita , Abbate Boris , Iacoviello Giuseppina , Evangelista Giovanna , Gilardi Maria Carla , Bondì Maria Luisa , Forte Giusi Irma
Published: July 2019

In breast cancer (BC) care, radiotherapy is considered an efficient treatment, prescribed both for controlling localized tumors or as a therapeutic option in case of inoperable, incompletely resected or recurrent tumors. However, approximately 90% of BC-related deaths are due to the metastatic tumor progression. Then, it is strongly desirable to improve tumor radiosensitivity using molecules with synergistic action. The main aim of this study is to develop curcumin-loaded solid nanoparticles (Cur-SLN) in order to increase curcumin bioavailability and to evaluate their radiosensitizing ability in comparison to free curcumin (free-Cur), by using an in vitro approach on BC cell lines. In addition, transcriptomic and metabolomic profiles, induced by Cur-SLN treatments, highlighted networks involved in this radiosensitization ability. The non tumorigenic MCF10A and the tumorigenic MCF7 and MDA-MB-231 BC cell lines were used. Curcumin-loaded solid nanoparticles were prepared using ethanolic precipitation and the loading capacity was evaluated by UV spectrophotometer analysis. Cell survival after treatments was evaluated by clonogenic assay. Dose–response curves were generated testing three concentrations of free-Cur and Cur-SLN in combination with increasing doses of IR (2–9 Gy). IC50 value and Dose Modifying Factor (DMF) was measured to quantify the sensitivity to curcumin and to combined treatments. A multi-“omic” approach was used to explain the Cur-SLN radiosensitizer effect by microarray and metobolomic analysis. We have shown the efficacy of the Cur-SLN formulation as radiosensitizer on three BC cell lines. The DMFs values, calculated at the isoeffect of SF = 50%, showed that the Luminal A MCF7 resulted sensitive to the combined treatments using increasing concentration of vehicled curcumin Cur-SLN (DMF: 1,78 with 10 µM Cur-SLN.) Instead, triple negative MDA-MB-231 cells were more sensitive to free-Cur, although these cells also receive a radiosensitization effect by combination with Cur-SLN (DMF: 1.38 with 10 µM Cur-SLN). The Cur-SLN radiosensitizing function, evaluated by transcriptomic and metabolomic approach, revealed anti-oxidant and anti-tumor effects. Curcumin loaded- SLN can be suggested in future preclinical and clinical studies to test its concomitant use during radiotherapy treatments with the double implications of being a radiosensitizing molecule against cancer cells, with a protective role against IR side effects.
Polymeric nanocapsular baicalin: Chemometric optimization, physicochemical characterization and mechanistic anticancer approaches on breast cancer cell lines
Authors: I. El-Gogary Riham , Gaber Sara A. Abdel , Nasr Maha
Published: July 2019

Baicalin is a multi-purpose flavonoid known for its anticancer properties, but its application is hindered by its low water solubility and bioavailability. Polymeric nanocapsules were proposed in this work as a promising system for enhancing baicalin delivery, and potentiating its anticancer properties. The characterization of nanocapsules was augmented with chemometric analysis, and the selected formulations were tested on two breast cancer cell lines (MCF-7 and MDA-MB-231), with mechanistic anticancer elucidation using MTT assay, confocal microscopy uptake, flow cytometry, mechanism of cell death, reactive oxygen species production, caspase 3/7 activity and death biomarker expression using quantitative real time PCR. Results showed that baicalin nanocapsules displayed favorable pharmaceutical properties; with the formulation variables affecting their properties elucidated using chemometric factorial analysis. Nanocapsules enhanced the anticancer activity of baicalin up to 216 times for MCF-7 cells and 31 times for MDA-MB-231 after 24 hr incubation. Cellular internalization of the fluorescently labeled nanocapsules was confirmed after 4 hr incubation for both cell lines. Apoptosis was the dominant cell death mechanism, with significant up-regulation of P53 in baicalin nanocapsules treated cells. Data here presented drive to further preclinical studies to investigate the delivery of baicalin polymeric nanocapsules and their anti-cancer activity.
Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis
Authors: Liu Yan , Zhong Guo-Chao , Tan Hao-Yang , Hao Fa-Bao , Hu Jie-Jun
Published: July 2019

Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. The present study aimed to clarify this issue. A systematic search of PubMed and Embase was conducted through October 2018. Studies providing risk estimates of NAFLD and mortality were included. A random-effects model was employed to calculate summary risk estimates. Subgroup analyses were performed to identify potential effect modifiers. Fourteen studies, involving 498501 subjects and 24234 deaths, were included. Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR) = 1.34; 95% confidence interval (CI) 1.17–1.54)]. The significantly positive association between NAFLD and all-cause mortality could not be modified by age, sex, follow-up duration, and adjustment for body mass index, diabetes, smoking or hypertension (all Pinteraction > 0.05), and remained in sensitivity analyses. No significant associations of NAFLD with CVD (HR = 1.13; 95% CI 0.92–1.38) and cancer (HR = 1.05; 95% CI 0.89–1.25) mortality were found. In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. These findings have important implications for decision making in public health and clinical practice, and highlight the urgency of developing effective treatments for NAFLD.
Stable InSe transistors with high-field effect mobility for reliable nerve signal sensing
Authors: Jiang Jianfeng , Li Jingxin , Li Yutao , Duan Jiazhzhi , Li Linshen , Tian Ye , Zong Zhihua , Zheng Haotian , Feng Xianjin , Li Qiqiang , Liu Hong , Zhang Yu , Ren Tian-Ling , Han Lin
Published: July 2019

Among two-dimensional layered semiconductors, indium selenide (InSe) is one of the most promising materials with absolute advantages in field-effect transistors (FETs) because of its high electron mobility and stable material properties. Some work has been performed to improve the mobility of InSe FETs. However, in practical applications, electrical stability of FETs is another essential factor to guarantee the performance of the electronic system. Here, we show a highly stable InSe FET with a field-effect mobility of 1200 cm2/V·s in the practical working regime. The bottom-gate staggered InSe FET was fabricated with a polymethyl methacrylate (PMMA)/HfO2 dual-layer gate dielectric and PMMA back-channel encapsulation. The hysteresis was maintained at 0.4 V after 30 days of storage under normal ambient conditions, and the threshold voltage shift was retained at 0.6 V with a gate stress VGS of 10 V, which represents the best electrical stability reported to date. Its high mobility and electrical stability enable reliable detection of the weak nerve action potential at a low power consumption. High-performance InSe FETs expand their promising applications in flexible and in situ real-time intelligent nerve action potential recording.
Visualizing hydrogen diffusion in magnetic film through magneto-optical Kerr effect
Authors: Chang Po-Chun , Chang Yun-Ying , Wang Wei-Hsiang , Lo Fang-Yuh , Lin Wen-Chin
Published: July 2019

The kinematics of hydrogen diffusion in nontransparent metallic materials is crucial to the hydrogen-sensing and -storage technology and remains a challenge. Alongside the conventional optical investigations, the hydrogen absorption-induced reversible changes of magnetic properties in ferromagnetic thin films provides a new method for visualization of hydrogen in solids. Here we monitor real-time hydrogen diffusion in a cobalt-palladium alloy (Co25Pd75) film using a magneto-optical Kerr microscope. The spatially resolved magneto-optical contrasted images provide a noninvasive method of monitoring hydrogen movement. Hydrogen diffusion follows Fick’s diffusion law, and a diffusion coefficient of 3 ± 2 × 10−12 m2/s is obtained. The diffusion velocity of the 2–4% hydrogen concentration fronts reaches 30 ± 15 nm/s in the uniform film area and increases to 50 ± 20 nm/s near a defect site. These results can be applied in detecting hydrogen diffusion in other spintronic materials, such as magnetic palladium-alloy thin films.
Antimicrobial Quaternary Ammonium Polymers for Biomedical Applications
Authors: Farah Shady
Published: July 2019

Microbial infection is a detrimental issue that can reduce the success of a wide range of biomedical implants. Several approaches are being developed to address this challenging obstacle. Cationic polymers, i.e. quaternary ammonium functionalized polymers have been reported repeatedly, with significant antimicrobial activity targeting broad spectrum of microorganisms through the disruption of the cell wall. Quaternary ammonium polymers or polymers modified with quaternary ammonium molecules possessing antimicrobial activity have been used as a part of self-sterilizing surfaces and composites, as well as additives addressing the need for antimicrobial activity or properties for a wide range of biomedical applications. In this chapter, an overview of the different antimicrobial polymers based on quaternary ammonium moieties is presented. Chemical structure, chemical modification, bioactivity and biomedical application are summarized and discussed.
A dissolvable hierarchical layered double hydroxide templated from porous zeolitic imidazolate framework-67 for dispersive solid phase extraction of bisphenol A
Authors: Ghani Milad
Published: July 2019

This is the first time that the in situ preparation of advanced extraction media based on a hierarchical layered double hydroxide (HLDH).
An electrochemical aptasensor for detection of lead ions using a screen-printed carbon electrode modified with Au/polypyrrole composites and toluidine blue
Authors: Ding Jina , Zhang Dongwei , Liu Yang , Yu Minglei , Zhan Xuejia , Zhang Dan , Zhou Pei
Published: July 2019

An aptasensor based on the aptamer of lead(ii) ions and the composites of Au nanoparticles and polypyrrole (Au@Py) was successfully fabricated.
Essential oil ofSchisandra chinensisameliorates cognitive decline in mice by alleviating inflammation
Authors: Xu Mengjie , Zhang Xiaoying , Ren Fangyi , Yan Tingxu , Wu Bo , Bi Kaishun , Bi Wenchuan , Jia Ying
Published: July 2019

In this study, we aimed to assess the possible impacts of essential oil (SEO) fromSchisandra chinensis(Turcz.) Baill. (S. chinensis) on mice with cognition impairment.
Maternal dietary resveratrol alleviates weaning-associated diarrhea and intestinal inflammation in pig offspring by changing intestinal gene expression and microbiota
Authors: Meng Qingwei , Sun Shishuai , Luo Zhang , Shi Baoming , Shan Anshan , Cheng Baojing
Published: July 2019

Maternal dietary resveratrol alters intestinal gene expression and microbiota in offspring.
Hierarchical assembly of hyaluronan coated albumin nanoparticles for pancreatic cancer chemoimmunotherapy
Authors: Hu Ying , Chen Xue , Xu Yingying , Han Xianru , Wang Mou , Gong Tao , Zhang Zhi-Rong , John Kao W. , Fu Yao
Published: July 2019

Pancreatic cancer is a highly malignant carcinoma with limited effective treatment options, resulting in a poor patient survival rate of less than 5%.
Construction and morphology of non-covalently double-crosslinked supramolecular polymer networks
Authors: Chen Senbin , Wang Ke , Geng Zhen , Chen Yu , Zheng Xihuang , Wang Huiying , Zhu Jintao
Published: July 2019

A straightforward synthesis of α-Ba, ω-TAP functionalized polymers, Ba-PnBuA-TAP, is reported, leading to the formation of double-crosslinked supramolecular networks driven via the sequential hydrogen-bonding association and metal-coordination.
Molecular superoxide radical photogeneration in cancer cells by dipyridophenazine iridium(iii) complexes
Authors: Novohradsky Vojtech , Vigueras Gloria , Pracharova Jitka , Cutillas Natalia , Janiak Christoph , Kostrhunova Hana , Brabec Viktor , Ruiz Jose , Kasparkova Jana
Published: July 2019

The switch from Type II to Type I photochemical mechanism by new Ir(iii) complexes for improved PDT of cancer under hypoxia is demonstrated.
Pd-Catalyzed intramolecular C–H activation and C–S formation to synthesize pyrazolo[5,1-b]benzothiazoles without an additional oxidant
Authors: Peng Yingyuan , He Qian , Zhang Xiaofei , Yang Chunhao
Published: July 2019

An efficient synthesis of pyrazolo[5,1-b]benzothiazole scaffold via Pd-catalyzed intramolecular C–H activation and C–S formation was developed.
Iodine-mediated synthesis of benzo[a]fluorenones from yne-enones
Authors: Akbar Sikkandarkani , Tamilarasan V. John , Srinivasan Kannupal
Published: July 2019

An iodine mediated synthesis of benzo[a]fluorenone derivatives from the chalcones derived from o-alkynylacetophenones and aromatic aldehydes is described.
A thermally activated delayed fluorescence exciplex to achieve highly efficient and stable blue and green phosphorescent organic light-emitting diodes
Authors: Dou Dehai , Wu Peng , Liao Zhangcheng , Hao Jian , Zhang Jianhua , Wang Zixing
Published: July 2019

A high energy TADF exciplex (415 nm) based on aza-spirobifluorene derivatives was demonstrated to achieve efficient and stable PhOLEDs.
3D printable SiO2 nanoparticle ink for patient specific bone regeneration
Authors: Roopavath Uday Kiran , Soni Raghav , Mahanta Urbashi , Deshpande Atul Suresh , Rath Subha Narayan
Published: July 2019

3D printing of a complex and irregular virtual defect using SiO2 nanoparticle and hydrogel composite ink for patient specific defect fabrication.
Growth of carbon dioxide whiskers
Authors: Both Avinash Kumar , Cheung Chin Li
Published: July 2019

Carbon dioxide (CO2) whiskers were reported to grow at low temperatures (−70 °C to −65 °C) and moderate pressure (4.4 to 1.0 bar).
A theoretical study on the dynamics of a compound vesicle in shear flow
Authors: Sinha Kumari Priti , Thaokar Rochish M.
Published: July 2019

The dynamical modes observed for a compound vesicle in a shear flow are represented on the nondimensional rotationalvs.extensional strengths and exhibits swinging and new modes of intermediate tumbling swinging and oscillatory relaxation to tank treading.
Manipulation of 2D carbon nanoplates with a core–shell structure for high-performance potassium-ion batteries
Authors: Li Dongjun , Cheng Xiaolong , Xu Rui , Wu Ying , Zhou Xuefeng , Ma Cheng , Yu Yan
Published: July 2019

Quasi-2D core–shell amorphous carbon/graphitic carbon nanoplates (AC@GC) are designed, and they exhibit synergistic properties that enable the construction of superior K-ion batteries.
Dendrimers and hyper-branched polymers interacting with clays: fruitful associations for functional materials
Authors: Caminade Anne-Marie , Beraa Abdellah , Laurent Régis , Delavaux-Nicot Béatrice , Hajjaji Mohamed
Published: July 2019

The interaction of dendrimers or hyper-branched polymers with clays produces different types of new materials.
Manipulating H-bonds in glassy dipolar polymers as a new strategy for high energy storage capacitors with high pulse discharge efficiency
Authors: Liu Jingjing , Li Meng , Zhao Yifei , Zhang Xiao , Lu Junyong , Zhang Zhicheng
Published: July 2019

The formation of H-bonds results in improved dielectric strength of glassy polystyrene-based polymers.
A universal method for quantitative analysis of triboelectric nanogenerators
Authors: Li Xiaoyi , Lau Tsz Him , Guan Dong , Zi Yunlong
Published: July 2019

A universal method is built for all kinds of TENGs, which can give quantitative analysis formulae.
A facile route to well-dispersed Ru nanoparticles embedded in self-templated mesoporous carbons for high-performance supercapacitors
Authors: Aftabuzzaman M. , Kim Chang Ki , Kowalewski Tomasz , Matyjaszewski Krzysztof , Kim Hwan Kyu
Published: July 2019

Ru-NPs-embedded self-templated mesoporous carbons were successfully prepared by a facile route. They show excellent electrochemical performance with very high specific gravimetric capacitance, good rate capability, and excellent long-term cycling stability.
Metal-free energy storage systems: combining batteries with capacitors based on a methylene blue functionalized graphene cathode
Authors: Zhang Yadi , An Yufeng , Wu Langyuan , Chen Heng , Li Zihan , Dou Hui , Murugadoss Vignesh , Fan Jincheng , Zhang Xiaogang , Mai Xianmin , Guo Zhanhu
Published: July 2019

Novel aqueous hybrid ion capacitors based on an MB functionalized graphene cathode and asymmetric electrolytes exhibited both improved energy density and power density.
The manipulation of substitutional defects for realizing high thermoelectric performance in Mg3Sb2-based Zintl compounds
Authors: Li Juan , Jia Fei , Zhang Shuai , Zheng Shuqi , Wang Boyi , Chen Liqiang , Lu Guiwu , Wu Liming
Published: July 2019

By optimizing the concentration of the substitutional defect PrMg1, Mg3.2Pr0.02Sb1.5Bi0.5 exhibits a peak zT value of 1.70 at 725 K.
Strong magnetic field-dual-assisted fabrication of heterogeneous sulfide-based hollow nanochain electrodes for high-rate supercapacitors
Authors: Yu Xing , Yu Jiali , Fautrelle Yves , Gagnoud Annie , Ren Zhongming , Lu Xionggang , Li Xi
Published: July 2019

A strong magnetic field was applied twice to synthesize one-dimensional hetero-Zn0.76Co0.24S/Co3S4/β-CoS1.097 hollow nanochain-based electrodes for high-rate supercapacitors.
Simple and cost effective fabrication of 3D porous core–shell Ni nanochains@NiFe layered double hydroxide nanosheet bifunctional electrocatalysts for overall water splitting
Authors: Cai Zhengyang , Bu Xiuming , Wang Ping , Su Wenqiang , Wei Renjie , Ho Johnny C. , Yang Junhe , Wang Xianying
Published: July 2019

Meticulously designed 3D porous core–shell Ni nanochains@NiFe LDH nanosheets bifunctional electrocatalysts outperform the state-of-the-art IrO2 (+)//Pt/C (−) electrodes and most of the reported LDH electrocatalysts for overall water splitting.
Solution-processed thin films of a charge transfer complex for ambipolar field-effect transistors
Authors: Salzillo Tommaso , Campos Antonio , Mas-Torrent Marta
Published: July 2019

Solution-deposited thin films of the charge transfer complexDBTTF–TCNQblended with polystyrene lead to ambipolar field-effect transistor devices.
Synthesis of an isomerically pure thienoquinoid for unipolar n-type conjugated polymers: effect of backbone curvature on charge transport performance
Authors: Guo Kai , Wu Botao , Jiang Yu , Wang Zhongli , Liang Ziqi , Li Yuning , Deng Yunfeng , Geng Yanhou
Published: July 2019

A polymer based on thienoquinoid showed unipolar n-type characteristics with an electron mobility of up to 0.45 cm2 V−1 s−1.
Hormone Replacement Therapy and Voice
Authors: Abitbol Jean
Published: July 2019

The purpose of this article is to update the management of the treatment of the female voice at perimenopause and menopause. Voice and hormones—these are 2 words that clash, meet, and harmonize. If we are to solve this inquiry, we shall inevitably have to understand the hormones, their impact, and the scars of time. The endocrine effects on laryngeal structures are numerous: The actions of estrogens and progesterone produce modification of glandular secretions. Low dose of androgens are secreted principally by the adrenal cortex, but they are also secreted by the ovaries. Their effect may increase the low pitch and decease the high pitch of the voice at menopause due to important diminution of estrogens and the privation of progesterone.

The menopausal voice syndrome presents clinical signs, which we will describe. I consider menopausal patients to fit into 2 broad types: the “Modigliani” types, rather thin and slender with little adipose tissue, and the “Rubens” types, with a rounded figure with more fat cells. Androgen derivatives are transformed to estrogens in fat cells. Hormonal replacement therapy should be carefully considered in the context of premenopausal symptom severity as alternative medicine. Hippocrates: “Your diet is your first medicine.”