bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic asymmetric acetalization of carboxylic acids for access to chiral phthalidyl ester prodrugs
Authors: Liu Yingguo , Chen Qiao , Mou Chengli , Pan Lutai , Duan Xiaoyong , Chen Xingkuan , Chen Hongzhong , Zhao Yanli , Lu Yunpeng , Jin Zhichao , Chi Yonggui Robin 
Published: April 2019

AbstractCarboxylic acids are common moieties in medicines. They can be converted to phthalidyl esters as prodrugs. Unfortunately, phthalidyl esters are now mostly prepared in racemic forms. This is not desirable because the two enantiomers of phthalidyl esters likely have different pharmacological effects. Here we address the synthetic challenges in enantioselective modification of carboxylic acids via asymmetric acetalizations. The key reaction step involves asymmetric addition of a carboxylic acid to the catalyst-bound intermediate. This addition step enantioselectively constructs a chiral acetal unit that lead to optically enriched phthalidyl esters. A broad range of carboxylic acids react effectively under mild and transition metal-free conditions. Preliminary bioactivity studies show that the two enantiomers of chlorambucil phthalidyl esters exhibit different anti-cancer activities to inhibit the growth of Hela cells. Our catalytic strategy of asymmetric acetalizations of carboxylic acids shall benefit future development of chiral phthalidyl ester prodrugs and related molecules.
Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα
Authors: Liang Ning , Damdimopoulos Anastasius , Goñi Saioa , Huang Zhiqiang , Vedin Lise-Lotte , Jakobsson Tomas , Giudici Marco , Ahmed Osman , Pedrelli Matteo , Barilla Serena , Alzaid Fawaz , Mendoza Arturo , Schröder Tarja , Kuiper Raoul , Parini Paolo , Hollenberg Anthony , Lefebvre Philippe , Francque Sven , Van Gaal Luc , Staels Bart , Venteclef Nicolas , Treuter Eckardt , Fan Rongrong 
Published: April 2019

AbstractObesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.
Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity
Authors: Lavarone Elisa , Barbieri Caterina M. , Pasini Diego 
Published: April 2019

AbstractThe Polycomb repressive complexes PRC1 and PRC2 act non-redundantly at target genes to maintain transcriptional programs and ensure cellular identity. PRC2 methylates lysine 27 on histone H3 (H3K27me), while PRC1 mono-ubiquitinates histone H2A at lysine 119 (H2Aub1). Here we present engineered mouse embryonic stem cells (ESCs) targeting the PRC2 subunits EZH1 and EZH2 to discriminate between contributions of distinct H3K27 methylation states and the presence of PRC2/1 at chromatin. We generate catalytically inactive EZH2 mutant ESCs, demonstrating that H3K27 methylation, but not recruitment to the chromatin, is essential for proper ESC differentiation. We further show that EZH1 activity is sufficient to maintain repression of Polycomb targets by depositing H3K27me2/3 and preserving PRC1 recruitment. This occurs in the presence of altered H3K27me1 deposition at actively transcribed genes and by a diffused hyperacetylation of chromatin that compromises ESC developmental potential. Overall, this work provides insights for the contribution of diffuse chromatin invasion by acetyltransferases in PRC2-dependent loss of developmental control.
Modulating the mechanism of electrocatalytic CO2 reduction by cobalt phthalocyanine through polymer coordination and encapsulation
Authors: Liu Yingshuo , McCrory Charles C. L. 
Published: April 2019

AbstractThe selective and efficient electrochemical reduction of CO2 to single products is crucial for solar fuels development. Encapsulating molecular catalysts such as cobalt phthalocyanine within coordination polymers such as poly-4-vinylpyridine leads to dramatically increased activity and selectivity for CO2 reduction. In this study, we use a combination of kinetic isotope effect and proton inventory studies to explain the observed increase in activity and selectivity upon polymer encapsulation. We provide evidence that axial-coordination from the pyridyl moieties in poly-4-vinylpyridine to the cobalt phthalocyanine complex changes the rate-determining step in the CO2 reduction mechanism accounting for the increased activity in the catalyst-polymer composite. Moreover, we show that proton delivery to cobalt centers within the polymer is controlled by a proton relay mechanism that inhibits competitive hydrogen evolution. These mechanistic findings provide design strategies for selective CO2 reduction electrocatalysts and serve as a model for understanding the catalytic mechanism of related heterogeneous systems.
A requirement for STAG2 in replication fork progression creates a targetable synthetic lethality in cohesin-mutant cancers
Authors: Mondal Gourish , Stevers Meredith , Goode Benjamin , Ashworth Alan , Solomon David A. 
Published: April 2019

AbstractCohesin is a multiprotein ring that is responsible for cohesion of sister chromatids and formation of DNA loops to regulate gene expression. Genomic analyses have identified that the cohesin subunit STAG2 is frequently inactivated by mutations in cancer. However, the reason STAG2 mutations are selected during tumorigenesis and strategies for therapeutically targeting mutant cancer cells are largely unknown. Here we show that STAG2 is essential for DNA replication fork progression, whereby STAG2 inactivation in non-transformed cells leads to replication fork stalling and collapse with disruption of interaction between the cohesin ring and the replication machinery as well as failure to establish SMC3 acetylation. As a consequence, STAG2 mutation confers synthetic lethality with DNA double-strand break repair genes and increased sensitivity to select cytotoxic chemotherapeutic agents and PARP or ATR inhibitors. These studies identify a critical role for STAG2 in replication fork procession and elucidate a potential therapeutic strategy for cohesin-mutant cancers.
Formation of colloidal alloy semiconductor CdTeSe magic-size clusters at room temperature
Authors: Gao Dong , Hao Xiaoyu , Rowell Nelson , Kreouzis Theo , Lockwood David J. , Han Shuo , Fan Hongsong , Zhang Hai , Zhang Chunchun , Jiang Yingnan , Zeng Jianrong , Zhang Meng , Yu Kui 
Published: April 2019

AbstractAlloy semiconductor magic-size clusters (MSCs) have received scant attention and little is known about their formation pathway. Here, we report the synthesis of alloy CdTeSe MSC-399 (exhibiting sharp absorption peaking at 399 nm) at room temperature, together with an explanation of its formation pathway. The evolution of MSC-399 at room temperature is detected when two prenucleation-stage samples of binary CdTe and CdSe are mixed, which are transparent in optical absorption. For a reaction consisting of Cd, Te, and Se precursors, no MSC-399 is observed. Synchrotron-based in-situ small angle X-ray scattering (SAXS) suggests that the sizes of the two samples and their mixture are similar. We argue that substitution reactions take place after the two binary samples are mixed, which result in the formation of MSC-399 from its precursor compound (PC-399). The present study provides a room-temperature avenue to engineering alloy MSCs and an in-depth understanding of their probable formation pathway.
A statistical atlas of cerebral arteries generated using multi-center MRA datasets from healthy subjects
Authors: Mouches Pauline , Forkert Nils D. 
Published: April 2019

AbstractMagnetic resonance angiography (MRA) can capture the variation of cerebral arteries with high spatial resolution. These measurements include valuable information about the morphology, geometry, and density of brain arteries, which may be useful to identify risk factors for cerebrovascular and neurological diseases at an early time point. However, this requires knowledge about the distribution and morphology of vessels in healthy subjects. The statistical arterial brain atlas described in this work is a free and public neuroimaging resource that can be used to identify vascular morphological changes. The atlas was generated based on 544 freely available multi-center MRA and T1-weighted MRI datasets. The arteries were automatically segmented in each MRA dataset and used for vessel radius quantification. The binary segmentation and vessel size information were non-linearly registered to the MNI brain atlas using the T1-weighted MRI datasets to construct atlases of artery occurrence probability, mean artery radius, and artery radius standard deviation. This public neuroimaging resource improves the understanding of the distribution and size of arteries in the healthy human brain.
High resolution paddy rice maps in cloud-prone Bangladesh and Northeast India using Sentinel-1 data
Authors: Singha Mrinal , Dong Jinwei , Zhang Geli , Xiao Xiangming 
Published: April 2019

AbstractKnowledge of where, when, and how much paddy rice is planted is crucial information for understating of regional food security, freshwater use, climate change, and transmission of avian influenza virus. We developed seasonal paddy rice maps at high resolution (10 m) for Bangladesh and Northeast India, typical cloud-prone regions in South Asia, using cloud-free Synthetic Aperture Radar (SAR) images from Sentinel-1 satellite, the Random Forest classifier, and the Google Earth Engine (GEE) cloud computing platform. The maps were provided for all the three distinct rice growing seasons of the region: Boro, Aus and Aman. The paddy rice maps were evaluated against the independent validation samples, and compared with the existing products from the International Rice Research Institute (IRRI) and the analysis of Moderate Resolution Imaging Spectroradiometer (MODIS) data. The generated paddy rice maps were spatially consistent with the compared maps and had a satisfactory accuracy over 90%. This study showed the potential of Sentinel-1 data and GEE on large scale paddy rice mapping in cloud-prone regions like tropical Asia.
Biodiversity loss in a Mediterranean ecosystem due to an extreme warming event unveils the role of an engineering gorgonian species
Authors: Verdura Jana , Linares Cristina , Ballesteros Enric , Coma Rafel , Uriz María J. , Bensoussan Nathaniel , Cebrian Emma 
Published: April 2019

AbstractStochastic perturbations can trigger major ecosystem shifts. Marine systems have been severely affected in recent years by mass mortality events related to positive thermal anomalies. Although the immediate effects in the species demography affected by mortality events are well known, information on the mid- to long-term effects at the community level is much less documented. Here, we show how an extreme warming event replaces a structurally complex habitat, dominated by long-lived species, by a simplified habitat (lower species diversity and richness) dominated by turf-forming species. On the basis of a study involving the experimental manipulation of the presence of the gorgonian Paramuricea clavata, we observed that its presence mitigated the effects of warming by maintaining the original assemblage dominated by macroinvertebrates and delaying the proliferation and spread of the invasive alga Caulerpa cylindracea. However, due to the increase of sediment and turf-forming species after the mortality event we hypothesize a further degradation of the whole assemblage as both factors decrease the recruitment of P.clavata, decrease the survival of encrusting coralligenous-dwelling macroinvertebrates and facilitate the spreading of C. cylindracea.
Relationship between Contact Pressure and Motion Artifacts in ECG Measurement with Electrostatic Flocked Electrodes Fabricated on Textile
Authors: Takeshita Toshihiro , Yoshida Manabu , Takei Yusuke , Ouchi Atsushi , Hinoki Akinari , Uchida Hiroo , Kobayashi Takeshi 
Published: April 2019

AbstractTo develop a wearable multi-lead electrocardiogram (ECG) measuring system, we fabricated the electrodes and wires by using electrostatic flocking technology on a textile. By using this technology, it was possible to fabricate many electrodes and wires, simultaneously. Also the flocked electrodes and wires had stretchability and washing resistance properties. To use dry electrodes, it is important to reduce the influence of motion artifacts (MAs). The results of the experiment with the skin phantom revealed that the contact pressure between the skin and the electrode is an important factor in MA reduction. Then, we conducted experiments with a human body to determine the relationship between the contact pressure and the MAs. Under the pressures of 200 Pa and 500 Pa, MAs were observed. Meanwhile, under the pressures of 1000 Pa, 2000Pa and 4000 Pa, the ECG signals under rest and deep breathing conditions were able to be measured without MAs. Considering the comfortability, the contact pressure from 1000 Pa to 2000 is preferable. Finally, we fabricated the wearable ECG measuring system and succeeded in measuring 18-lead ECG signals. The measured ECG waveform is in good agreement with the ECG waveform measured by a commercial system.
Trends of polyphenolics and anthocyanins accumulation along ripening stages of wild edible fruits of Indian Himalayan region
Authors: Belwal Tarun , Pandey Aseesh , Bhatt Indra D. , Rawal Ranbeer S. , Luo Zisheng 
Published: April 2019

AbstractWild fruits are important food resources that provide health promoting nutraceutical components, which vary with ripening stages. In present study, five wild edible fruits of Indian Himalayan Region i.e.,Myrica esculenta,Berberis asiatica,Rubus ellipticus,Pyracantha crenulataandMorus albawere examined for their nutraceutical potential at different ripening stages. The results of present study showed that polyphenolic concentration decreased whereas anthocyanin level increased with fruit ripening, however few species and compounds showed different trends. Among the tested fruit species, unripe fruits ofB. asiaticafollowed byM. esculentawere found to be the best for harvesting polyphenolics (especially catechin), while ripen fruits ofM. esculentafollowed byB. asiaticawere found the best for anthocyanin (cyanin and delphinidin) extraction. The results from this study can be effectively used by the harvesters, consumers, traders and food and nutraceutical industries to harness maximum nutraceutical potential depending on the preferred compounds and ripening stages of these species.
Contrast Agent Enhanced Multimodal Photoacoustic Microscopy and Optical Coherence Tomography for Imaging of Rabbit Choroidal and Retinal Vessels in vivo
Authors: Nguyen Van Phuc , Li Yanxiu , Qian Wei , Liu Bing , Tian Chao , Zhang Wei , Huang Ziyi , Ponduri Arjun , Tarnowski Madison , Wang Xueding , Paulus Yannis M. 
Published: April 2019

AbstractMultimodal imaging with photoacoustic microscopy (PAM) and optical coherence tomography (OCT) can be an effective method to evaluate the choroidal and retinal microvasculature. To improve the efficiency for visualizing capillaries, colloidal gold nanoparticles (AuNPs) have been applied as a multimodal contrast agent for both OCT and PAM imaging by taking advantage of the strong optical scattering and the strong optical absorption of AuNPs due to their surface plasmon resonance. Ultra-pure AuNPs were fabricated by femtosecond laser ablation, capped with polyethylene glycol (PEG), and administered to 13 New Zealand white rabbits and 3 Dutch Belted pigmented rabbits. The synthesized PEG-AuNPs (20.0 ± 1.5 nm) were demonstrated to be excellent contrast agents for PAM and OCT, and do not demonstrate cytotoxicity to bovine retinal endothelial cells in cell studies. The image signal from the retinal and choroidal vessels in living rabbits was enhanced by up to 82% for PAM and up to 45% for OCT, respectively, by the administered PEG-AuNPs, which enables detection of individual blood vessels by both imaging modalities. The biodistribution study demonstrated the AuNP accumulated primarily in the liver and spleen. Histology and TUNEL staining did not indicate cell injury or death in the lung, liver, kidney, spleen, heart, or eyes up to seven days after AuNP administration. PEG-AuNPs offer an efficient and safe contrast agent for multimodal ocular imaging to achieve improved characterization of microvasculature.
Impact of Fluorosis on the Tensile Bond Strength of Metal Brackets and the Prevalence of Enamel Microcracks
Authors: Trakinienė Giedrė , Petravičiūtė Gabrielė , Smailienė Dalia , Narbutaitė Julija , Armalaitė Justė , Lopatienė Kristina , Šidlauskas Antanas , Trakinis Tomas 
Published: April 2019

AbstractThe objective of this in vitro study was to determine the effects of dental fluorosis on the tensile bond strength of metal brackets bonded to human teeth and to evaluate the changes in the tooth enamel surface after debonding. The study sample consisted of 68 recently extracted human upper premolars, which were divided into 2 groups: the fluorosis group (34 fluorosed teeth) and the control group (34 healthy teeth). Identical premolar metal brackets were bonded on the buccal surfaces of the teeth. Both groups were submitted to a tension test using a universal testing machine. The number and length of the enamel microcracks in the buccal surface of each tooth were determined before bracket bonding and after debonding using a stereomicroscope. The percentage adhesive remnant index (PARI) was calculated after debonding. The results showed that the tensile bond strength (TBS) of brackets bonded to fluorosed teeth was 21.08% lower than that of brackets bonded to healthy teeth (p < 0.0001). The length of the enamel microcracks on fluorosed teeth increased by 47.4% after debonding, whereas the control group showed an increase of only 12.6%. The PARI showed lower values for fluorosed teeth in comparison to the control group (p = 0.047). In conclusion, dental fluorosis has a negative impact on tensile bond strength and the length of microcracks formed after bracket debonding.
Association between serum high-sensitivity C-reactive protein levels and erectile dysfunction: a cross-sectional study of Chinese male population
Authors: Li Wenying , Chen Kai , Zhang Jinping , Wang Xiaohong , Xu Guangyu , Zhu Yinghong , Lv Yan 
Published: April 2019

AbstractInflammation has been known to affect endothelial function and is involved in the progression of erectile dysfunction (ED). Thus, our present study was conducted to investigate the association between inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and ED in a Chinese male population. A total of 1515 participants with anthropometric measurements, serum analyses and hs-CRP values available were included in our cross-sectional study. Data involving socioeconomic and lifestyle factors were also collected. ED was assessed by the 5-item International Index Erectile Function (IIEF-5), and hs-CRP levels were measured by the immunoturbidimetric assay. Logistic regression was applied to estimate the association between the serum hs-CRP and the risk of ED, and receiver operating characteristics (ROC) curve analysis was performed to identify the predictive value of hs-CRP. Serum hs-CRP levels were significantly higher in ED patients, and increased progressively with the incremental severity of ED (P < 0.001 for trend). In the multivariate-adjusted model, men in the highest quartile of hs-CRP level versus those in the lowest quartile had a 50% increased likelihood for ED (OR = 1.50; 95% CI = 1.08–2.08). When subjects were stratified by age, the risk of ED was more prominently in the middle-aged and elderly men. Based on the ROC analysis, serum hs-CRP has a poor diagnostic value for ED with an AUC of 0.58 (95% CI: 0.56–0.61) but has a good diagnostic performance for differentiating severe ED (AUC: 0.79; 95% CI: 0.77–0.81). Our study indicates that increased serum hs-CRP levels are associated with the severity of ED and an increased ED risk in a Chinese male population. These findings suggest that hs-CRP may be of value as an inflammatory marker for the assessment of ED risk and may play an important role in the etiology of ED.
Usefulness of serum microRNA as a predictive marker of recurrence and prognosis in biliary tract cancer after radical surgery
Authors: Akazawa Yu , Mizuno Shoichi , Fujinami Norihiro , Suzuki Toshihiro , Yoshioka Yusuke , Ochiya Takahiro , Nakamoto Yasunari , Nakatsura Tetsuya 
Published: April 2019

AbstractBiliary tract cancer (BTC) is an aggressive type of malignant tumour. Even after radical resection, the risk of recurrence is still high, resulting in a poor prognosis. Here, we investigated the usefulness of serum miRNAs as predictive markers of recurrence and prognosis for patients with BTC after radical surgery using 66 serum samples that were collected at three time points from 22 patients with BTC who underwent radical surgery. Using microarray analysis, we successfully identified six specific miRNAs (miR-1225-3p, miR-1234-3p, miR1260b, miR-1470, miR-6834-3p, and miR-6875-5p) associated with recurrence and prognosis of BTC after radical surgery. In addition, using a combination of these miRNAs, we developed a recurrence predictive index to predict recurrence in patients with BTC after operation with high accuracy. Patients having higher index scores (≥ cut-off) had significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with lower index scores (<cut-off). Furthermore, the index was an independent factor related to RFS and OS by univariate and multivariate analyses using a Cox hazard proportional model. Overall, our results provided compelling evidence for the potential usefulness of specific serum miRNAs as effective predictive tools for recurrence and prognosis in patients with BTC who underwent radical surgery.
Mediatory roles of leukotriene B4 receptors in LPS-induced endotoxic shock
Authors: Kwon Sun-Young , Ro MyungJa , Kim Jae-Hong 
Published: April 2019

AbstractSepsis, a systemic inflammatory response syndrome caused by infection, is the most common disease in patients treated in intensive care units. Endotoxic shock, the most critical form of sepsis, is caused by gram-negative bacterial infection. However, the detailed mechanism of endotoxic shock remains unclear. In the present study, we observed that the production of leukotriene B4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (HETE), inflammatory lipid mediators acting on LTB4 receptors (BLT1 and BLT2), was significantly upregulated in peritoneal lavage fluid (PF) and serum from an LPS-induced endotoxic shock mouse model. Furthermore, BLT1/2-dependent signaling pathways mediated the expression of IL-17, IL-6, and IL-1β, key cytokines for the development of endotoxic shock, via NF-κB activation in the LPS-induced endotoxic shock mouse model. Additionally, inhibition of BLT1/2 significantly attenuated inflammation and tissue damage associated with endotoxic shock and enhanced the survival rate of mice with this inflammatory complication. Together, these results suggest that LTB4 receptors play critical mediatory roles in the development of endotoxic shock. Our findings point to LTB4 receptors as potential therapeutic targets for the treatment of endotoxic shock.