bluuebunny/crossref_metadata_2025 huggingface dataset:
Iturin A‐like lipopeptides from Bacillus subtilis trigger apoptosis, paraptosis, and autophagy in Caco‐2 cells
Authors: Zhao Haobin , Xu Xiaoguang , Lei Shuzhen , Shao Dongyan , Jiang Chunmei , Shi Junling , Zhang Yawen , Liu Li , Lei Shuzhen , Sun Hui , Huang Qingsheng
Published: September 2018

This study revealed that iturin A‐like lipopeptides produced by Bacillus subtillis induced both paraptosis and apoptosis in heterogeneous human epithelial colorectal adenocarcinoma (Caco‐2) cells. Autophagy was simultaneously induced in Caco‐2 cells treated with iturin A‐like lipopeptides at the early stage and inhibited at the later stage. A western blot analysis showed that the lipopeptides induced apoptosis in Caco‐2 cells via a mitochondrial‐dependent pathway, as indicated by upregulated expression of the apoptotic genes bax and bad and downregulated expression of the antiapoptotic gene bcl‐2. The induction of paraptosis in Caco‐2 cells was indicated by the occurrence of many cytoplasmic vacuoles accompanied by endoplasmic reticulum (ER) dilatation and mitochondrial swelling and dysfunction. ER stress also occurred with significant increases in reactive oxygen species and Ca2+ levels in cells. Autophagy was detected by a transmission electron microscopy analysis and by upregulated expression of LC3‐II and downregulated expression of LC3‐I. The inhibition of autophagy at the later stage was shown by upregulated expression of p62. This study revealed the capability of iturin A‐like B. subtilis lipopeptides to simultaneously execute antitumor potential via multiple pathways.
Opioids in Breast Milk: Pharmacokinetic Principles and Clinical Implications
Authors: Ito Shinya
Published: September 2018

Safety of maternal drug therapy during breastfeeding may be assessed from estimated levels of drug exposure of the infant through milk. Pharmacokinetic (PK) principles predict that the lower the clearance is, the higher the infant dose via milk will be. Drugs with low clearance (<1 mL/[kg·min]) are likely to cause an infant exposure level greater than 10% of the weight‐adjusted maternal dose even if the milk‐to‐plasma concentration ratio is 1. Most drugs cause relatively low‐level exposure below 10% of the weight‐adjusted maternal dose, but opioids require caution because of their potential for severe adverse effects. Furthermore, substantial individual variations of drug clearance exist in both mother and infant, potentially causing drug accumulation over time in some infants even if an estimated dose of the drug through milk is small. Such PK differences among individuals are known not only for codeine and tramadol through pharmacogenetic variants of CYP2D6 but also for non‐CYP2D6 substrate opioids including oxycodone, indicating difficulties of eliminating PK uncertainty by simply replacing an opioid with another. Overall, opioid use for pain management during labor and delivery and subsequent short‐term use for 2‐3 days are compatible with breastfeeding. In contrast, newly initiated and prolonged maternal opioid therapy must follow a close monitoring program of the opioid‐naive infants. Until more safety data become available, treatment duration of newly initiated opioids in the postpartum period should be limited to 2‐3 days in unsupervised outpatient settings. Opioid addiction treatment with methadone and buprenorphine during pregnancy may continue into breastfeeding, but infant conditions must be monitored.
Probiotics in Disease Prevention and Treatment
Authors: Liu Yuying , Tran Dat Q. , Rhoads J. Marc
Published: September 2018

Few treatments for human diseases have received as much investigation in the past 20 years as probiotics. In 2017, English‐language meta‐analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, and hepatic encephalopathy in adults. The strongest evidence in favor of probiotics lies in the prevention or treatment of 5 disorders: necrotizing enterocolitis, acute infectious diarrhea, acute respiratory tract infections, antibiotic‐associated diarrhea, and infant colic. Probiotic mechanisms of action include the inhibition of bacterial adhesion; enhanced mucosal barrier function; modulation of the innate and adaptive immune systems (including induction of tolerogenic dendritic cells and regulatory T cells); secretion of bioactive metabolites; and regulation of the enteric and central nervous systems. Future research is needed to identify the optimal probiotic and dose for specific diseases, to address whether the addition of prebiotics (to form synbiotics) would enhance activity, and to determine if defined microbial communities would provide benefit exceeding that of single‐species probiotics.
Molecular imaging with neural training of identification algorithm (neural network localization identification)
Authors: Nelson A. J. , Hess S. T.
Published: September 2018

Superresolution localization microscopy strongly relies on robust identification algorithms for accurate reconstruction of the biological systems it is used to measure. The fields of machine learning and computer vision have provided promising solutions for automated object identification, but usually rely on well represented training sets to learn object features. However, using a static training set can result in the learned identification algorithm making mistakes on data that is not well represented by the training set. Here, we present a method for training an artificial neural network without providing a training set in advance. This method uses the data to be analyzed, and the fitting algorithm to train an artificial neural network tailored to that data set. We show that the same artificial neural network can learn to identify at least two types of molecular emissions: the regular point spread functions (PSFs), and the astigmatism PSF. Simulations indicate that this method can be extremely reliable in extracting molecular emission signatures. Additionally, we implemented the artificial neural network calculation to be performed on a graphics processing unit (GPU) for massively parallelized calculation which drastically reduces the time required for the identification process. By implementing the neural identification on a GPU, we allow this method of identification to be used in a real time analysis algorithm.

Research highlights

Here, we present a machine learning algorithm for identifying point‐spread functions without the need for an a priori training set. We show that this method can detect over 90% of molecules with less than 1% false positive identification in simulations. We further show that because this algorithm does not make assumptions of about the shape of molecular emission, it is compatible with models beyond the symmetric 2D Gaussian.
Influence of environmental and genetic factors on 3‐hydoxypropionaldehyde production by Lactobacillus reuteri
Authors: Ortiz‐Rivera Yuridia , Sánchez‐Vega Rogelio , Acosta‐Muñiz Carlos Horacio , Gutiérrez‐Méndez Néstor , León‐Félix Josefina , Sepulveda David R.
Published: September 2018

The influence of environmental factors such as glycerol concentration, time of production, presence of Escherichia coli, and two different strains of Lactobacillus reuteri (ATCC 55730 and ATCC 53608) on 3‐hydroxypropionaldehyde (3‐HPA) production was analyzed. Additionally, the influence of those factors on gene expression in the 3‐HPA production pathway was evaluated. The genes studied were GldC, cbiP, and Lreu_1734. The results of this study showed that the principal environmental factors that influence 3‐HPA production are glycerol concentration and Lactobacillus reuteri strain. As glycerol concentration increased, 3‐HPA content increased. The greatest 3‐HPA concentration (56.6 mM ±5.99) was achieved by L. reuteri ATCC 55730. Gene expression was also affected by environmental factors. Factor that showed the greatest influence were also strain and glycerol concentration. The genes cbiP, GldC, and Lreu_1734 had basal gene expression in glycerol absence; however, glycerol regulated its expression. Glycerol induced overexpression of cbiP and GldC genes (Strain ATCC 53608), probably to ensure its efficient utilization. On the contrary, glycerol concentration suppressed Lre_1734 expression in both analyzed strains, as a mechanism for 3‐HPA accumulation. Down‐regulation was observed in all the genes tested in strain ATCC 55730, probably due to feedback inhibition by 3‐HPA.
A comparative study on the effect of soundscape and landscape on tourism experience
Authors: He Mang , Li Jingwen , Li Jun , Chen Huiyi
Published: September 2018

This paper explores how soundscape and landscape influences tourism experience by the cases of Leshan Giant Buddha and Mount Emei, China. Results show that there is a mutually positive relationship between soundscape perception and landscape perception; soundscape perception indirectly affect tourism experience through “the congruence between soundscape and landscape”; and only landscape can directly affect shallow experience. This study also brings implications for tourism research and practice: soundscape should be given more attention as it can significantly affect the tourism experience, and relevant industrial sectors can improve tourism experiences through the design or control of soundscape.
Nasal Reconstruction Using a Customized Three‐Dimensional–Printed Stent for Congenital Arhinia: Three‐Year Follow‐up
Authors: Jung Jin Woo , Ha Dong‐Heon , Kim Boo Young , Seo Bommie F. , Han Hyun Ho , Kim Do Hyun , Rhie Jong‐Won , Kim Sung Won , Cho Dong‐Woo
Published: September 2018

A male Mongolian child with a complete congenital absence of both nose and nasal passage had a poor survival prognosis due to respiratory distress. To enable his survival, a new nose capable of conferring respiratory function was constructed. Following reconstructive surgery, an absence of mucoepithelium in the nasal passage can lead to rhinostenosis. To avoid this complication, a custom‐made nasal silicone stent was created using three‐dimensional (3D) printing technology in conjunction with the patient's computed tomography data. The stent was implanted for 2 months to maintain the shape and size of the nasal passage. At 2 months after stent implantation, the mucoepithelium tissue in the passage had successfully regenerated with no immune reaction. Three years after stent removal, respiratory function, nasal passage structure, and external nose shape were maintained without additional medical care. These results indicate the successful nasal reconstruction in an arhinia patient using a customized, 3D‐printed nasal stent. Laryngoscope, 129:582–585, 2019
Trophic niche partitioning of dominant North‐Atlantic krill species, Meganyctiphanes norvegica, Thysanoessa inermis, and T. raschii
Authors: Cabrol J. , Trombetta T. , Amaudrut S. , Aulanier F. , Sage R. , Tremblay R. , Nozais C. , Starr M. , Plourde S. , Winkler G.
Published: September 2018

Different krill species have a pivotal position in many marine food webs by both preying upon several trophic levels and being forage species for consumers. Within these food webs, different krill species coexist, though it remains unclear what mechanisms allow for the coexistence, for instance, of northern krill species in subarctic environments. Here, we hypothesize that the stable coexistence of sympatric krill species is based on trophic niche partitioning related to seasonal trade‐offs between their respective food preferences, their energy needs, and prey availability. To test our hypothesis, we analyzed the diets, feeding selectivity, and lipid composition of three coexisting northern krill species (Meganyctiphanes norvegica, Thysanoessa inermis, and Thysanoessa raschii) throughout 1 yr using a multimarker approach. We assessed lipid classes, fatty acids, and stable isotope signatures of krill and potential food sources (27 groups, from phytoplankton to lipid‐rich copepods) to elucidate seasonal variation of niche utilization. Results revealed strong trophic niche separation occurring at a very fine trophic scale (species level) throughout the year. The three krill species showed different degrees of food specialization rather than being purely opportunistic as classically proposed. Feeding on copepod prey was important to accumulate energy reserves for overwintering and subsequent rebuilding of energy reserves. Energy reserve utilization might reduce potential competition for the limited available resources, especially under low food conditions.
The Role of Liver Transplantation in Propionic Acidemia
Authors: Quintero Jesús , Molera Cristina , Juamperez Javier , Redecillas Susanna , Meavilla Silvia , Nuñez Raquel , García Camila , del Toro Mireia , Garcia Ángels , Ortega Juan , Segarra Óscar , de Carpi Javier Martin , Bilbao Itxarone , Charco Ramon
Published: September 2018

Despite optimal medical treatment and strict low‐protein diet, the prognosis of propionic acidemia (PA) patients is generally poor. We aim to report our experience with liver transplantation (LT) in the management of PA patients. Six patients with PA received a LT at a mean age of 5.2 years (1.3‐7.5 years). The indications for LT were frequent metabolic decompensations in the first 4 patients and preventative in the last 2 patients. Two patients presented hepatic artery thromboses that were solved through an interventional radiologist approach. These patients showed a very high procoagulant state that was observed by thromboelastography. Arterial vasospasm without thrombus was observed in 2 patients during the LT surgery. In order to avoid hepatic artery thrombosis, an arterial conduit from the recipient aorta to the hepatic artery of the donor was used in the fifth patient. After LT, patients presented improvement in propionyl byproducts without complete normalization, but no decompensations have been observed. In conclusion, LT could be a good therapeutic option to improve the metabolic control and the quality of life of PA patients. Improved surgical strategies along with new techniques of interventional radiology allow us to perform the LT minimizing the complications derived from the higher risk of hepatic artery thrombosis.
Analysis of the use of environmentally friendly corrosion inhibitors for mild steel in a carbon dioxide saturated chloride solution via experimental design
Authors: Vieira Casanova Monteiro Mariana , Pessu Frederick , Barker Richard , Antônio da Cunha Ponciano Gomes José , Neville Anne
Published: September 2018

In the oil and gas industry, carbon dioxide (CO2) gas dissolved in produced fluids can cause both general and localized corrosion of carbon steel pipelines due to the speciation of carbonic acid. To mitigate corrosion, the injection of inhibitors into the production fluid is one of the most commonly used methods. However, recent changes in regulations has resulted in a requirement for the development of new corrosion inhibitors that conform to European regulations. This paper presents a full two‐level factorial experimental design approach to study individual effects of environmentally friendly classed inhibitor components (phosphate ester, imidazoline, and quaternary amine derivatives) as combined inhibitors and their interactive effects on carbon steel corrosion processes in CO2‐saturated 3.5 wt.% NaCl brine. Through the application of in situ electrochemical monitoring, post‐test interferometry, and scanning electron microscopy (SEM) it was possible to determine the influence of each component within the blends and their effect on both general and localized corrosion. Based on 24 h experiments, the phosphate ester derivative reduced general corrosion rate in all blends; imidazoline derivatives reduced the uniform corrosion rate only when it was at the high level in the blend; and the quaternary amine derivative promoted pitting on the surface.
Effects of Silk Degumming Process on Physicochemical, Tensile, and Optical Properties of Regenerated Silk Fibroin
Authors: Nultsch Kira , Bast Livia K. , Näf Muriel , Yakhlifi Salima El , Bruns Nico , Germershaus Oliver
Published: September 2018

Sericin removal from silk (degumming) affects material characteristics of silk fibroin (SF). Sodium carbonate is most commonly used for degumming, but numerous alternative methods are available. Herein, a systematic comparison of degumming methods is provided. Sodium carbonate, sodium oleate, trypsin, and ionic liquid are used, and materials are characterized regarding mass loss, SF content, molecular integrity of SF, refractive index, and tensile properties. Complete degumming is achieved within 30 min of using sodium carbonate, but results in significant reduction of molecular weight, shift toward less acidic charge variants, and reduction of yield‐ and rupture force. Sodium oleate and trypsin are inefficient and negatively affect tensile properties, while ionic liquid shows good efficiency and marginal degradation of SF but also reduced yield‐ and rupture force. Refractive index is not affected by degumming. These results allow rational selection of the degumming method and tuning of SF properties for biomedical applications.
Idolizing “My Love from the Star”: Idol attachment and fanaticism of luxury brands
Authors: Cheah Isaac , Liang Johan , Phau Ian
Published: September 2018

This study examines the influence of idol attachment and consumer fanaticism on consumers’ attitude toward celebrity product placement of luxury fashion brands in Korean television dramas. A 2 × 2 research design was used to examine two different product categories (fashion apparel vs. fashion accessories) and two celebrities (Kim Soo Hyun vs. Jun Ji‐Hyun). Respondents were screened and limited to those who were aware of the Korean television drama My Love from the Star. The findings show that the gender of celebrity and the category of product placement have differential impacts on viewers or fans’ attitudes and intention toward the product placement.
CCDC85B promotes non‐small cell lung cancer cell proliferation and invasion
Authors: Feng Yangyang , Gao Yue , Yu Juanhan , Jiang Guiyang , Zhang Xiupeng , Lin Xuyong , Han Qiang , Rong Xuezhu , Xu Hongtao , Li Qingchang , Qiu Xueshan , Wang Enhua
Published: September 2018

Coiled‐coil domain containing 85 B (CCDC85B) is involved in diverse biological processes; however, its expression patterns and functions in human cancers are yet unknown. The present study demonstrated that the expression of CCDC85B in the cytoplasm of the non‐small cell lung cancer (NSCLC) tumor cells was significantly higher compared to adjacent normal lung tissues (P < 0.05). Furthermore, CCDC85B expression correlated with advanced TNM stage (P = 0.004) and positive regional lymph node metastasis (P = 0.009) of NSCLC. In addition, in A549 and H1299 lung cancer cell lines, the overexpression of CCDC85B promoted cell proliferation and invasion, while siRNA‐mediated CCDC85B knockdown exhibited opposite effects. CCDC85B promoted AKT and GSK3β phosphorylation and upregulated the levels of active β‐catenin, Wnt targets c‐myc, cyclin D1, and MMP7. Besides, the CCDC85B‐induced upregulation of phosphorylated GSK3β and active β‐catenin was rescued following the treatment with PI3 K inhibitor, LY294002. In conclusion, CCDC85B was associated with NSCLC progression as it promoted the proliferation and invasion of lung cancer cells through activated AKT/GSK3β/β‐catenin oncogenic signaling pathway. Therefore, CCDC85B might serve as a novel target for NSCLC treatment.
Alternating Thalamic Deep Brain Stimulation for Essential Tremor: A Trial to Reduce Habituation
Authors: Seier Mara , Hiller Amie , Quinn Joseph , Murchison Charles , Brodsky Matthew , Anderson Shannon
Published: September 2018

Background

DBS in the ventral intermediate nucleus (VIM) of the thalamus has been a revolutionary treatment for patients with essential tremor (ET) by reducing tremor. Unfortunately, some patients develop habituation to DBS and thus experience reduced efficacy and loss of tremor control. There are no standardized methods of addressing habituation to DBS. We propose alternating stimulation patterns as a way to reduce habituation.

Methods

This was a randomized, placebo‐controlled trial for patients with VIM DBS for ET. Patients were randomized to either experimental treatment arm of alternating stimulation patterns on a weekly basis or standard care arm of continuous stimulation settings for 12 weeks. Primary outcome was change in the performance subscale of The Essential Tremor Rating Assessment Scale (TETRAS), which was performed at initial visit and 12‐week follow‐up. Secondary outcome included change in the activities of daily living subscale of TETRAS.

Results

Twenty‐two patients were enrolled in the trial, and 16 were analyzed at follow‐up. Experimental treatment subjects displayed sustained tremor control compared to standard care, as measured by the change in TETRAS performance subscale (–0.6 vs. 6.7 point change, respectively) with a 7.3 difference between the arms (P = 0.006).

Conclusion

Alternating stimulation patterns on a weekly basis for ET patients with VIM DBS reduced habituation in this pilot study. This study suggests that exposure to different stimulation groups may maintain better tremor control compared to constant stimulation parameters.
Hazmat risk area assessment by atmospheric dispersion modelling using Latin hypercube sampling with weather ensemble
Authors: Sigg Robert , Lindgren Petter , von Schoenberg Pontus , Persson Leif , Burman Jan , Grahn Håkan , Brännström Niklas , Björnham Oscar
Published: September 2018

Atmospheric dispersion modelling is always encumbered by errors and uncertainties originating from different aspects of the weather description as well as the source and dispersion models. Even so, the typical results from these kinds of studies are limited to one realization with no measure of uncertainties in either the temporal or spatial dimensions. This result is then to be interpreted as the most probable outcome given the current information. However, in many situations this limited result and the presentation thereof are far from satisfying and in the worst case even dangerously misleading. To address this shortcoming, this work presents a well‐established method for uncertainty investigation in simulations called Latin hypercube sampling in combination with a weather ensemble which results in an alternative way of estimating the resulting risk area as a function of weather forecast time from a statistical perspective. The main idea with this approach is to use the entire probability distribution of the simulation parameters instead of only one value as is the case in traditional methodology. This is a useful concept that provides additional and valuable information for decision makers.
Global positioning systems meteorology over Morocco: accuracy assessment and comparison of zenith tropospheric delay from global positioning systems and radiosondes
Authors: Hdidou Fatima Zahra , Mordane Soumia , Sbii Siham
Published: September 2018

Global positioning systems (GPSs) have become a powerful remote sensing tool to estimate the water vapour in the troposphere. This study describes the operational processing of the Moroccan ground‐based GPS meteorology stations. It presents the evaluation of the accuracy of zenith tropospheric delay (ZTD). The accuracy is evaluated first in relation to the International Global Navigation Satellite System Service (IGS) final products, and second by comparison to equivalent values derived from radiosonde profiles. The comparison of near‐real‐time ZTD with the IGS final product shows a bias of −1 mm with a standard deviation of 6 mm. The comparison with radiosondes shows a bias of −2.82 mm and a standard deviation of 14.01 mm. Also, the comparison of GPS ZTD and radiosonde ZTD time series over almost 1 year (2016) shows good agreement and a seasonal signal with higher values of ZTD in summer.
Radar‐derived parameters in hail‐producing storms and the estimation of hail occurrence in Romania using a logistic regression approach
Authors: Stefan Sabina , Barbu Nicu
Published: September 2018

This study investigated the radar‐derived parameters in hail‐producing storms and compared two hail‐detection approaches in order to select the optimal method for real‐time hail detection for the southern part of Romania. A statistical analysis of radar parameters was made, and the thresholds for radar‐deriver parameters in hail‐producing storms were determined. In addition, the hail storms’ life cycle and diurnal and seasonal cycles of hail occurrence were investigated. The first algorithm developed in this study was based on the logistic regression model (LRM); the second one on the vertically integrated liquid (VIL) density algorithm. These algorithms were tested for the convective seasons (May–September) of 2014 and 2015. For the construction of the LRM, the composite reflectivity (CR), VIL and echo‐top high (ET) were used as predictors for the probability of hail occurrence determination for 43 hail events observed at the synoptic station located in the radar‐coverage area. The obtained statistics showed a marked diurnal cycle of hail occurrence with a maximum in the afternoon hours (1500–1800 LT), and the highest occurrence frequency of hail falls was in June. The results revealed that 93% of hail events occurred with 60 dBZ CR, 87% with 13 km ET, 100% with 55 kg/m2 VIL and 100% with 4.5 g/m3 VIL density. For the two hail‐detection methods’ performance comparison, a two‐by‐two contingency table was constructed and several statistical scores calculated. The LRM algorithm performed better than the VIL density algorithm.
On statistical nowcasting of road surface temperature
Authors: Yin Zhicong , Hadzimustafic Jasmina , Kann Alexander , Wang Yong
Published: September 2018

In this study, multiple linear regression (MLR) and the generalized additive model (GAM) approaches were used to build statistical models for 6 hr nowcasts of road surface temperature (RST) in the northeast of Vienna, Austria. GAMs were more suitable for historical analysis, particularly for decomposing the terms to identify the different influences of the meteorological covariates on RST. By contrast, for RST nowcasting, the simpler and more robust MLR models are recommended, with better applicability for real‐time operational runs. In MLR models, the forecasted air temperature was the most prominent predictor, followed by the measured RST. In independent testing, the MLR models showed better prediction skill, with daily root‐mean‐square error (RMSE) around 1°C. In accordance with the linear correlativity, the MLR models were built with more predictors for daytime than at night but still generated a larger RMSE at midday. Furthermore, the MLR models could reproduce the correct diurnal variation and could forecast RST below freezing point better than above 0°C. Four case studies, i.e. snowy, cold front, cloudy and sunny, were diagnosed in detail. The predicted RSTs were close to the measurements and depicted the trend well, including the persistent and rapid cooling (warming) and correct diurnal variation.
Flip‐Flop Index: Quantifying revision stability for fixed‐event forecasts
Authors: Griffiths Deryn , Foley Michael , Ioannou Ioanna , Leeuwenburg Tennessee
Published: September 2018

The degree to which a forecast changes from one issue time to the next is an interesting aspect of a forecast system. Weather forecasters report that they are reluctant to change a forecast if they judge there is a risk of it being changed back again. They believe such instability detracts from the message being delivered and are reluctant to use automated guidance which they perceive as having lack of stability. A Flip‐Flop Index was developed to quantify this characteristic of revisions of fixed‐event forecasts. The index retains physically meaningful units, has a simple definition and does not penalize a sequence of forecasts that show a trend, which is important when assessing forecasts where a trend can be interpreted as a forecast becoming more confident with a shorter lead time. The Flip‐Flop Index was used to compare the stability of sequences of automated guidance with the official Australian Bureau of Meteorology forecasts, which are prepared manually. The results show that the forecasts for chance of rain from the automated guidance are often more stable than the official, manual forecasts. However, the official forecasts for maximum temperature are more stable than those based on automated guidance. The Flip‐Flop Index is independent of observations and does not measure skill, but it can play a complementary role in characterizing and evaluating a forecasting system.
Goji Berry Modulates Gut Microbiota and Alleviates Colitis in IL‐10‐Deficient Mice
Authors: Kang Yifei , Yang Guan , Zhang Shuming , Ross Carolyn F. , Zhu Mei‐Jun
Published: September 2018

Scope

This study examines the beneficial effects of Goji berry against spontaneous colitis and its prebiotic role in IL‐10‐deficient mice.

Methods

IL‐10‐deficient mice are assigned to a standard rodent diet (control) or a control diet supplemented with Goji (1% of dry feed weight) for 10 weeks, at which point colonic tissues and fecal contents are collected.

Results

Goji supplementation decreases colonic pathobiological scores and mRNA expression of Il17a and Tgfb1, while it enhances Muc1 expression and fecal IgA content. Illumina MiSeq sequencing reveals that Goji supplementation increases Actinobacteria phylum, resulting in a bloom of Bifidobacteria in gut microbiota. Additionally, dietary Goji promotes butyrate‐producing bacteria including Lachnospiraceae‐Ruminococcaceae family and Roseburia spp. under Clostridium cluster XIVa. Furthermore, butyrate‐producers Clostridium leptum and its dominant constituent Fecalibacterium prazusnitzii are markedly increased in the Goji group. Moreover, the gene‐encoding butyryl‐coenzyme A CoA transferase, a key enzyme responsible for butyrate synthesis in butyrate‐producing bacteria, is increased sixfold in the fecal samples of Goji group associated with increased fecal butyrate content.

Conclusion

Data collectively show that dietary Goji results in the blooming of Bifidobacteria and butyrate‐producing bacteria. These bacteria may cross‐feed each other, conferring preventative effects against colitis in IL‐10‐deficient mice.
Imaging of a high concentration of iron labeled cells with positive contrast in a rat knee
Authors: Magnitsky Sergey , Pickup Stephan , Garwood Michael , Idiyatullin Djaudat
Published: September 2018

Purpose

The sweep imaging with Fourier transformation (SWIFT) imaging technique has been shown to provide positive contrast from diluted cell suspensions labeled with super‐paramagnetic iron oxide (SPIO) in a tissue, as an alternative to T2*‐weighted imaging. Here we demonstrate a variation of the SWIFT technique that yields a hyperintense signal from a concentrated cell suspension. The proposed technique provides minimal background signal from host tissue and facilitates visualization of injected cells.

Methods

The proton resonance frequency and linewidth were determined for SPIO solutions of different concentrations. The original SWIFT sequence was modified and a dual saturation Gaussian shape RF pulse with ~200 Hz bandwidth was incorporated into the acquisition protocol to suppress host tissue and fat signals. This modification of the original acquisition protocol permits the detection of a hyperintense signal from grafted cells with minimal background signal from the host tissue.

Results

SPIO particles not only induce broadening of NMR line‐width but also an initiate proton resonance frequency shift. This shift is linearly proportional to the concentration of the iron oxide particles and induced by the bulk magnetic susceptibility of SPIOs. The shift of the resonance frequency of iron labeled cells allowed us effectively suppress the host tissues with saturation RF pulse to improve MRI detection of grafted cells.

Conclusions

Iron oxide particles increase the resonance frequency of water proton signal. This shift permitted us to add the tissue/fat saturation RF pulse into the original SWIFT acquisition protocol and detect distinct hyperintense signals from grafted cells with minimal background signal from the host tissue.
Screening for Fabry disease and Hereditary ATTR amyloidosis in idiopathic small‐fiber and mixed neuropathy
Authors: Samuelsson Kristin , Radovic Ana , Press Rayomand , Auranen Mari , Ylikallio Emil , Tyynismaa Henna , KäRppä Mikko , Veteläinen Matilda , Peltola Niina , Mellgren Svein Ivar , Mygland Åse , Tallaksen Chantal , Andersen Henning , Terkelsen Astrid Juhl , Fontain Freja , Hietaharju Aki
Published: September 2018

Introduction: In this study we assessed the value of genetic screening for Fabry disease (FD) and hereditary ATTR amyloidosis in patients with idiopathic small‐fiber neuropathy (SFN) or mixed neuropathy in a clinical setting. Methods: This was a Nordic multicenter study with 9 participating centers. Patients with idiopathic SFN or mixed neuropathy were included. Genetic sequencing of the TTR and GLA genes was performed. Results: There were 172 patients enrolled in the study. Genetic screening was performed in 155 patients. No pathogenic mutations in the TTR gene were found. A single patient had a possible pathogenic variant, R118C, in the GLA gene, but clinical investigation showed no firm signs of FD. Discussion: Screening for hereditary ATTR amyloidosis and FD in patients with idiopathic SFN or mixed neuropathy without any additional disease‐specific symptoms or clinical characteristics in a Nordic population appears to be of little value in a clinical setting. Muscle Nerve 59:354–357, 2019
Hepatitis B virus large surface protein is priming for hepatocellular carcinoma development via induction of cytokinesis failure
Authors: Musa Julian , Li Jing , Grünewald Thomas GP
Published: September 2018

Chronic hepatitis B virus (HBV) infection is a main risk factor for development of liver cirrhosis and hepatocellular carcinoma (HCC). Although HBV vaccination and antiviral therapy lead to substantial risk reduction for HCC development, it is evident that both can reduce, but not completely eliminate the risk. High serum levels of HBV surface antigen (HBsAg) were shown to predict disease progression of chronic HBV infection in patients harboring low viral load, and in line with this, HBV surface proteins were shown to exert oncogenic functions. As HBsAg seroclearance is infrequently achieved in patients who have undergone antiviral therapy, it is necessary to gain further insights into molecular mechanisms of HBsAg seroclearance failure after antiviral therapy and HCC development mediated by HBV surface proteins. A recent study published in this journal has shown that the HBsAg large surface protein (LHBs) contributes to HCC development by inducing cytokinesis failure and consequent aneuploidy via induction of DNA damage and polo‐like kinase 1 (PLK1)‐mediated G2/M checkpoint failure in hepatocytes. Inhibition of PLK1 by a PLK1‐specific small molecule inhibitor was shown to restore G2/M checkpoint in vitro and to reduce tumor burden in vivo. The initial LHBs‐induced hepatocyte aneuploidy may give rise to further aneuploidy and thereby lead to self‐propagating cycles of chromosomal instability driving intra‐tumor heterogeneity and clonal cancer evolution. Thus, LHBs‐induced cytokinesis failure may be a priming event for HCC development. In conclusion, the study not only provides further mechanistic insights into the oncogenic role of LHBs, but also identifies a potential target to interfere with the vicious circle of LHBs‐induced aneuploidy, which may be especially useful in patients showing failure of HBsAg seroclearance after antiviral therapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Bone morphogenetic protein receptor signal transduction in human disease
Authors: Gomez‐Puerto Maria Catalina , Iyengar Prasanna Vasudevan , García de Vinuesa Amaya , ten Dijke Peter , Sanchez‐Duffhues Gonzalo
Published: September 2018

Bone morphogenetic proteins (BMPs) are secreted cytokines that were initially discovered on the basis of their ability to induce bone. Several decades of research have now established that these proteins function in a large variety of physiopathological processes. There are about 15 BMP family members, which signal via three transmembrane type II receptors and four transmembrane type I receptors. Mechanistically, BMP binding leads to phosphorylation of the type I receptor by the type II receptor. This activated heteromeric complex triggers intracellular signaling that is initiated by phosphorylation of receptor‐regulated SMAD1, 5, and 8 (also termed R‐SMADs). Activated R‐SMADs form heteromeric complexes with SMAD4, which engage in specific transcriptional responses. There is convergence along the signaling pathway and, besides the canonical SMAD pathway, BMP‐receptor activation can also induce non‐SMAD signaling. Each step in the pathway is fine‐tuned by positive and negative regulation and crosstalk with other signaling pathways. For example, ligand bioavailability for the receptor can be regulated by ligand‐binding proteins that sequester the ligand from interacting with receptors. Accessory co‐receptors, also known as BMP type III receptors, lack intrinsic enzymatic activity but enhance BMP signaling by presenting ligands to receptors. In this review, we discuss the role of BMP receptor signaling and how corruption of this pathway contributes to cardiovascular and musculoskeletal diseases and cancer. We describe pharmacological tools to interrogate the function of BMP receptor signaling in specific biological processes and focus on how these agents can be used as drugs to inhibit or activate the function of the receptor, thereby normalizing dysregulated BMP signaling. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Synthesis and nanoimprinting of high refractive index and highly transparent polythioethers based on thiol‐ene click chemistry
Authors: Nakabayashi Kazuhiro , Sobu Shigeki , Kosuge Yuji , Mori Hideharu
Published: September 2018

This work demonstrates the UV nanoimprinting lithography (UV‐NIL) of high refractive index and highly transparent polythioethers based on thiol‐ene click chemistry. Herein, 9,9‐bis(3‐mercaptopropylphenylether)fluorene (BMPF) is designed as a new thiol monomer with a high refractive index, high transparency, and good processability for UV‐NIL. Colorless polythioethers are synthesized from BMPF and ene monomers under mild thiol‐ene click reaction conditions. Excellent transmittance (96%) of 400 nm light is observed in all the polymer films and high refractive index values of 1.5972–1.6382 are attained. UV‐NIL using thiol‐ene photopolymerization affords polymer nanoimprinting patterns with various features on the order of 100–500 nm without any fractures. To the best of our knowledge, this is the first report on UV‐NIL of high refractive index and highly transparent polymers. Through proper monomer and polymer design, novel polythioethers with suitable glass transition temperature (T
g) values are developed with high refractive index, high transparency, and good UV‐NIL processability. Furthermore, UV‐NIL based on thiol‐ene click chemistry is accomplished at the nanoscale. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2175–2182
Modular synthesis of photodegradable polymers with different sensitive wavelengths as UV/NIR responsive nanocarriers
Authors: Li Lei , Wu Yuhuan , Du Fu‐Sheng , Li Zi‐Chen
Published: September 2018

We report the modular and facile synthesis of three novel polymers able to photodegrade by UV and visible light via the Passerini multicomponent polymerizations of 1,6‐hexanedioic acid and 1,6‐diisocyanohexane with 5‐methoxy‐2‐nitrobenzaldehyde (M2), 4,5‐dimethoxy‐2‐nitrobenzaldehyde (M3) or 7‐(N,N‐diethylamino)‐4‐formylcoumarin (M4) respectively. This synthetic strategy takes the advantage of the in situ formation of a photolabile chromophore via the Passerini reaction of an aromatic aldehyde with an acid and an isocyanide, thus it is a versatile approach to regulating the photochemical property of the photolabile chromophores by just changing the aldehyde structure. Importantly, two polymers (P3 and P4) even exhibit NIR degradability due to the two‐photon absorption, and their nanoparticles formulated by the single emulsion method have been used as the NIR‐responsive nanocarriers for hydrophobic dyes. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 334–341
Highly oriented and ordered microstructures in block copolymer films
Authors: Zhao Wei , Zhang Yi , Wang Xiao , Hu Xiaowen , Liu Feng , Russell Thomas P. , Zhou Guofu
Published: September 2018

Block copolymer (BCP) films with long‐range lateral ordering and orientation are crucial for many applications. Here, we report a simple, versatile strategy based on a solution casting procedure, to produce millimeter thick film of BCPs with highly oriented nanostructures. Transmission electron microscope (TEM), small angle X‐ray scattering (SAXS), and Hansen solubility parameters were used to study the morphology and interactions of the system. A variety of BCP‐solvent pairs were investigated. Factors including set‐up geometry, BCP characteristics, solvent evaporation, surface tension, and interactions, such as solvent‐BCP, solvent‐substrate, and BCP‐substrate were examined. A mechanism is proposed to describe the observed long‐range lateral ordering and orientation in films up to 1 mm in thickness. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 1369–1375
In situ multiscale study of deformation heterogeneities in polylactide‐based materials upon drawing: Influence of initial crystallinity and plasticization
Authors: Brüster Berit , Martin Arnaud , Bardon Julien , Koutsawa Yao , Bernstorff Sigrid , Raquez Jean‐Marie , André Stéphane , Dubois Philippe , Addiego Frédéric
Published: September 2018

This work aims at identifying defects called deformation heterogeneities developing in polylactide (PLA)‐based materials upon drawing at room temperature. The influence of the initial crystallinity and of the plasticization methodology (physical blending vs. reactive blending) on the type of defect is also investigated. Defects are characterized in situ by (a) calculating the volume strain from digital image correlation (DIC), (b) measuring their surface density from optical microscopy, and (c) assessing their scattering invariant from small‐angle X‐ray scattering. Complementary structural analyses are done by microcomputed X‐ray tomography and atomic force microscopy. Drawing is accompanied by crazing in the case of low‐crystalline PLA, cracking in the case of annealed PLA, no defect in the case of plasticized PLA by physical blending, and shear bands and cracking in the case of plasticized PLA by reactive blending. These observations are discussed based on the initial structural features of the materials. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 1452–1468
Reinforcement of a dodecylacrylate plasma polymer by admixture of a diacrylate or a dimethacrylate cross‐linker
Authors: Bardon Julien , Martin Arnaud , Fioux Philippe , Amari Tassadit , Mertz Gregory , Delmée Maxime , Ruch David , Roucoules Vincent
Published: September 2018

Coatings have been deposited from acrylates and methacrylates mixtures by means of an aerosol assisted atmospheric plasma process. The reference coating precursor is dodecyl acrylate (DOCA). In order to improve the coatings mechanical properties, one diacrylate and one dimethacrylate are added to DOCA in the precursor mixture. It is expected that they act as cross‐linking agents, thus modifying the coatings macromolecular structure and improving the coating mechanical properties. The influence of cross‐linkers concentration on the coatings properties is investigated. An improvement of coatings scratch resistance when the concentration of cross‐linkers increases in the mixture is observed, but the effect on coatings structure is different between the diacrylate and the dimethacrylate.
Evaluation of the anticancer and anti‐metastasis effects of novel synthetic sodium channel blockers in prostate cancer cells in vitro and in vivo
Authors: Wang Jiajia , Lu Zongliang , Wu Changpeng , Li Yanwu , Kong Ya , Zhou Rui , Shi Kun , Guo Jing , Li Na , Liu Jie , Song Wei , Wang He , Zhu Mingxing , Xu Hongxia
Published: September 2018

Background

Voltage‐gated sodium channels (VGSCs) are involved in several cellular processes related to cancer cell growth and metastasis, including adhesion, proliferation, apoptosis, migration, and invasion. We here in investigated the effects of S0154 and S0161, two novel synthetic sodium channel blockers (SCBs), on human prostate cancer cells (PC3, DU145, and LnCaP) and a prostate cancer xenograft model.

Methods

The MTT assay was used to assess the anticancer effects of SCBs in PC3, DU145, and LnCaP cells. Sodium indicator and glucose uptake assays were used to determine the effects of S0154 and S0161 in PC3 cells. The impact of these SCBs on the proliferation, cell cycle, apoptosis, migration, and invasion of PC3 cells were determined using a CFDA‐SE cell proliferation assay, cell cycle assay, annexin V‐FITC apoptosis assay, transwell cell invasion assay, and wound‐healing assay, respectively. The protein expression levels of Nav1.6, Nav1.7, CDK1, cyclin B1, MMP2, MMP9 in PC3 cells were analysis by Western blotting. The in vivo anticancer activity was evaluated using a PC3 xenograft model in nude mice.

Results

S0154 and S0161 both showed anticancer and anti‐metastatic effects against prostate cancer cells and significantly inhibited cell viability, with IC50 values in the range of 10.51‐26.60 μmol/L (S0154) and 5.07‐11.92 μmol/L (S0161). Both compounds also increased the intracellular level of sodium, inhibited the protein expression of two α subunits of VGSCs (Nav1.6 and Nav1.7), and caused G2/M phase cell cycle arrest, with no or minor effects on cell apoptosis. Concentrations of 5 and 10 μmol/L of S0154 and S0161 significantly decreased the glucose uptake of PC3 cells. The compounds also inhibited the proliferation of PC3 cells and decreased their invasion in transwell assays. Furthermore, S0161 exerted antitumor activity in an in vivo PC3 xenograft model in nude mice, inhibiting the growth of the tumors by about 51% compared to the control group.

Conclusions

These results suggest that S0154 and S0161 have anticancer and anti‐metastasis effects in prostate cancer cells both in vitro and in vivo, supporting their further development as potential therapeutic agents for prostate cancer.