bluuebunny/crossref_metadata_2025_split huggingface dataset:
GATA6 promotes epithelial-mesenchymal transition and metastasis through MUC1/β-catenin pathway in cholangiocarcinoma
Authors: Deng Xiang , Jiang Peng , Chen Jian , Li Jianwei , Li Dajiang , He Yu , Jiang Yan , Zhang Yujun , Xu Shuangnian , Li Xi , Wang Shuguang , Tian Feng 
Published: October 2020

AbstractGATA6 acts as an oncogene or tumour suppressor in different cancers. Previously, we found that aberrant expression of GATA6 promoted metastasis in cholangiocarcinoma (CCA). However, the mechanism by which GATA6 promotes metastasis in CCA is unclear. In the present study, we aimed to investigate the role of GATA6 in CCA cell epithelial–mesenchymal transition (EMT). Our results showed that GATA6 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. GATA6 promoted EMT and metastasis in CCA cells in vitro and in vivo based on knockdown and overexpression analyses. ChIP-sequencing data revealed that MUC1 is a novel downstream target of GATA6. GATA6 upregulated MUC1 expression through binding to both the 1584 and 1456 GATA-motifs in the promoter region and enhancing its transcription by luciferase reporter assays and point-mutant assays. MUC1 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. In addition, MUC1 promoted EMT in CCA cells based on knockdown and overexpression analyses. Moreover, MUC1 knockdown significantly abrogated the GATA6-induced EMT in CCA cells, indicating that MUC1 promoted EMT through upregulating MUC1 in CCA cells. β-Catenin is a putative transcriptional coactivator that regulates EMT in cancers. Our data showed that MUC1 expression was positively associated with nuclear β-catenin expression in 91 CCA samples. MUC1 upregulated nuclear β-catenin expression in CCA cells. Moreover, MUC1 bound to β-catenin in CCA cells based on protein immunoprecipitation analyses. MUC1 knockdown significantly decreased the binding of MUC1 to β-catenin, and thereby decreased nuclear β-catenin protein levels in CCA cells, indicating that MUC1 bound to β-catenin and increased its nuclear expression in CCA cells. Together, our results show that GATA6 promotes EMT through MUC1/β-catenin pathway in CCA, indicating potential implications for anti-metastatic therapy.
Single crystalline quaternary sulfide nanobelts for efficient solar-to-hydrogen conversion
Authors: Wu Liang , Wang Qian , Zhuang Tao-Tao , Li Yi , Zhang Guozhen , Liu Guo-Qiang , Fan Feng-Jia , Shi Lei , Yu Shu-Hong 
Published: October 2020

AbstractAlthough solar-driven water splitting on semiconductor photocatalysts is an attractive route for hydrogen generation, there is a lack of excellent photocatalysts with high visible light activity. Due to their tunable bandgaps suitable for superior visible-light absorption, copper-based quaternary sulfides have been the important candidates. Here, we first assessed the preferred facet of wurtzite Cu-Zn-In-S for photocatalytic hydrogen evolution reaction using the relevant Gibbs free energies determined by first principle calculation. We then developed a colloidal method to synthesize single crystalline wurtzite Cu-Zn-In-S nanobelts (NBs) exposing (0001) facet with the lowest reaction Gibbs energy, as well as Cu-Zn-Ga-S NBs exposing (0001) facet. The obtained single crystalline Cu-Zn-In-S and Cu-Zn-Ga-S NBs exhibit superior hydrogen production activities under visible-light irradiation, which is composition-dependent. Our protocol represents an alternative surface engineering approach to realize efficient solar-to-chemical conversion of single crystalline copper-based multinary chalcogenides.
Computational optical imaging with a photonic lantern
Authors: Choudhury Debaditya , McNicholl Duncan K. , Repetti Audrey , Gris-Sánchez Itandehui , Li Shuhui , Phillips David B. , Whyte Graeme , Birks Tim A. , Wiaux Yves , Thomson Robert R. 
Published: October 2020

AbstractThe thin and flexible nature of optical fibres often makes them the ideal technology to view biological processes in-vivo, but current microendoscopic approaches are limited in spatial resolution. Here, we demonstrate a route to high resolution microendoscopy using a multicore fibre (MCF) with an adiabatic multimode-to-single-mode “photonic lantern” transition formed at the distal end by tapering. We show that distinct multimode patterns of light can be projected from the output of the lantern by individually exciting the single-mode MCF cores, and that these patterns are highly stable to fibre movement. This capability is then exploited to demonstrate a form of single-pixel imaging, where a single pixel detector is used to detect the fraction of light transmitted through the object for each multimode pattern. A custom computational imaging algorithm we call SARA-COIL is used to reconstruct the object using only the pre-measured multimode patterns themselves and the detector signals.
Aberrant methylation underlies insulin gene expression in human insulinoma
Authors: Karakose Esra , Wang Huan , Inabnet William , Thakker Rajesh V. , Libutti Steven , Fernandez-Ranvier Gustavo , Suh Hyunsuk , Stevenson Mark , Kinoshita Yayoi , Donovan Michael , Antipin Yevgeniy , Li Yan , Liu Xiaoxiao , Jin Fulai , Wang Peng , Uzilov Andrew , Argmann Carmen , Schadt Eric E. , Stewart Andrew F. , Scott Donald K. , Lambertini Luca 
Published: October 2020

AbstractHuman insulinomas are rare, benign, slowly proliferating, insulin-producing beta cell tumors that provide a molecular “recipe” or “roadmap” for pathways that control human beta cell regeneration. An earlier study revealed abnormal methylation in the imprinted p15.5-p15.4 region of chromosome 11, known to be abnormally methylated in another disorder of expanded beta cell mass and function: the focal variant of congenital hyperinsulinism. Here, we compare deep DNA methylome sequencing on 19 human insulinomas, and five sets of normal beta cells. We find a remarkably consistent, abnormal methylation pattern in insulinomas. The findings suggest that abnormal insulin (INS) promoter methylation and altered transcription factor expression create alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation. Finally, NFaT transcription factors, rather than the canonical PDX1 enhancer complex, are predicted to drive INS transactivation.
Phase synchronization of fluid-fluid interfaces as hydrodynamically coupled oscillators
Authors: Um Eujin , Kim Minjun , Kim Hyoungsoo , Kang Joo H. , Stone Howard A. , Jeong Joonwoo 
Published: October 2020

AbstractHydrodynamic interactions play a role in synchronized motions of coupled oscillators in fluids, and understanding the mechanism will facilitate development of applications in fluid mechanics. For example, synchronization phenomenon in two-phase flow will benefit the design of future microfluidic devices, allowing spatiotemporal control of microdroplet generation without additional integration of control elements. In this work, utilizing a characteristic oscillation of adjacent interfaces between two immiscible fluids in a microfluidic platform, we discover that the system can act as a coupled oscillator, notably showing spontaneous in-phase synchronization of droplet breakup. With this observation of in-phase synchronization, the coupled droplet generator exhibits a complete set of modes of coupled oscillators, including out-of-phase synchronization and nonsynchronous modes. We present a theoretical model to elucidate how a negative feedback mechanism, tied to the distance between the interfaces, induces the in-phase synchronization. We also identify the criterion for the transition from in-phase to out-of-phase oscillations.
Topaz-Denoise: general deep denoising models for cryoEM and cryoET
Authors: Bepler Tristan , Kelley Kotaro , Noble Alex J. , Berger Bonnie 
Published: October 2020

AbstractCryo-electron microscopy (cryoEM) is becoming the preferred method for resolving protein structures. Low signal-to-noise ratio (SNR) in cryoEM images reduces the confidence and throughput of structure determination during several steps of data processing, resulting in impediments such as missing particle orientations. Denoising cryoEM images can not only improve downstream analysis but also accelerate the time-consuming data collection process by allowing lower electron dose micrographs to be used for analysis. Here, we present Topaz-Denoise, a deep learning method for reliably and rapidly increasing the SNR of cryoEM images and cryoET tomograms. By training on a dataset composed of thousands of micrographs collected across a wide range of imaging conditions, we are able to learn models capturing the complexity of the cryoEM image formation process. The general model we present is able to denoise new datasets without additional training. Denoising with this model improves micrograph interpretability and allows us to solve 3D single particle structures of clustered protocadherin, an elongated particle with previously elusive views. We then show that low dose collection, enabled by Topaz-Denoise, improves downstream analysis in addition to reducing data collection time. We also present a general 3D denoising model for cryoET. Topaz-Denoise and pre-trained general models are now included in Topaz. We expect that Topaz-Denoise will be of broad utility to the cryoEM community for improving micrograph and tomogram interpretability and accelerating analysis.
Stress-induced RNA–chromatin interactions promote endothelial dysfunction
Authors: Calandrelli Riccardo , Xu Lixia , Luo Yingjun , Wu Weixin , Fan Xiaochen , Nguyen Tri , Chen Chien-Ju , Sriram Kiran , Tang Xiaofang , Burns Andrew B. , Natarajan Rama , Chen Zhen Bouman , Zhong Sheng 
Published: October 2020

AbstractChromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.
MYB61 is regulated by GRF4 and promotes nitrogen utilization and biomass production in rice
Authors: Gao Yihong , Xu Zuopeng , Zhang Lanjun , Li Shance , Wang Shaogan , Yang Hanlei , Liu Xiangling , Zeng Dali , Liu Qiaoquan , Qian Qian , Zhang Baocai , Zhou Yihua 
Published: October 2020

AbstractNitrogen (N) is a macronutrient that boosts carbon (C) metabolism and plant growth leading to biomass accumulation. The molecular connection between nitrogen utilization efficiency (NUE) and biomass production remains unclear. Here, via quantitative trait loci analysis and map-based cloning, we reveal that natural variation at the MYB61 locus leads to differences in N use and cellulose biogenesis between indica and japonica subspecies of rice. MYB61, a transcriptional factor that regulates cellulose synthesis, is directly regulated by a known NUE regulator GROWTH-REGULATING FACTOR4 (GRF4), which coordinates cellulosic biomass production and N utilization. The variation at MYB61 has been selected during indica and japonica domestication. The indica allele of MYB61 displays robust transcription resulting in higher NUE and increased grain yield at reduced N supply than that of japonica. Our study hence unravels how C metabolism is linked to N uptake and may provide an opportunity to reduce N use for sustainable agriculture.
Structural analysis reveals TLR7 dynamics underlying antagonism
Authors: Tojo Shingo , Zhang Zhikuan , Matsui Hiroyuki , Tahara Masahiro , Ikeguchi Mitsunori , Kochi Mami , Kamada Mami , Shigematsu Hideki , Tsutsumi Akihisa , Adachi Naruhiko , Shibata Takuma , Yamamoto Masaki , Kikkawa Masahide , Senda Toshiya , Isobe Yoshiaki , Ohto Umeharu , Shimizu Toshiyuki 
Published: October 2020

AbstractToll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases.
Highly efficient and air-stable Eu(II)-containing azacryptates ready for organic light-emitting diodes
Authors: Li Jiayi , Wang Liding , Zhao Zifeng , Sun Boxun , Zhan Ge , Liu Huanyu , Bian Zuqiang , Liu Zhiwei 
Published: October 2020

AbstractDivalent europium 5d-4ftransition has aroused great attention in many fields, in a way of doping Eu2+ions into inorganic solids. However, molecular Eu2+complexes with 5d-4ftransition are thought to be too air-unstable to explore their applications. In this work, we synthesized four Eu2+-containing azacryptates EuX2-Nn(X = Br, I,n = 4, 8) and systematically studied the photophysical properties in crystalline samples and solutions. Intriguingly, the EuX2-N8complexes exhibit near-unity photoluminescence quantum yield, good air-/thermal-stability and mechanochromic property (X = I). Furthermore, we proved the application of Eu2+complexes in organic light-emitting diodes (OLEDs) with high efficiency and luminance. The optimized device employing EuI2-N8as emitter has the best performance as the maximum luminance, current efficiency, and external quantum efficiency up to 25470 cd m−2, 62.4 cd A−1, and 17.7%, respectively. Our work deepens the understanding of structure-property relationship in molecular Eu2+complexes and could inspire further research on application in OLEDs.
Long-range exciton diffusion in molecular non-fullerene acceptors
Authors: Firdaus Yuliar , Le Corre Vincent M. , Karuthedath Safakath , Liu Wenlan , Markina Anastasia , Huang Wentao , Chattopadhyay Shirsopratim , Nahid Masrur Morshed , Nugraha Mohamad I. , Lin Yuanbao , Seitkhan Akmaral , Basu Aniruddha , Zhang Weimin , McCulloch Iain , Ade Harald , Labram John , Laquai Frédéric , Andrienko Denis , Koster L. Jan Anton , Anthopoulos Thomas D. 
Published: October 2020

AbstractThe short exciton diffusion length associated with most classical organic semiconductors used in organic photovoltaics (5-20 nm) imposes severe limits on the maximum size of the donor and acceptor domains within the photoactive layer of the cell. Identifying materials that are able to transport excitons over longer distances can help advancing our understanding and lead to solar cells with higher efficiency. Here, we measure the exciton diffusion length in a wide range of nonfullerene acceptor molecules using two different experimental techniques based on photocurrent and ultrafast spectroscopy measurements. The acceptors exhibit balanced ambipolar charge transport and surprisingly long exciton diffusion lengths in the range of 20 to 47 nm. With the aid of quantum-chemical calculations, we are able to rationalize the exciton dynamics and draw basic chemical design rules, particularly on the importance of the end-group substituent on the crystal packing of nonfullerene acceptors.
21-nt phasiRNAs direct target mRNA cleavage in rice male germ cells
Authors: Jiang Pengfei , Lian Bi , Liu Changzhen , Fu Zeyu , Shen Yi , Cheng Zhukuan , Qi Yijun 
Published: October 2020

AbstractIn grasses, phased small interfering RNAs (phasiRNAs), 21- or 24-nucleotide (nt) in length, are predominantly expressed in anthers and play a role in regulating male fertility. However, their targets and mode of action on the targets remain unknown. Here we profile phasiRNA expression in premeiotic and meiotic spikelets as well as in purified male meiocytes at early prophase I, tetrads and microspores in rice. We show that 21-nt phasiRNAs are most abundant in meiocytes at early prophase I while 24-nt phasiRNAs are more abundant in tetrads and microspores. By performing highly sensitive degradome sequencing, we find that 21-nt phasiRNAs direct target mRNA cleavage in male germ cells, especially in meiocytes at early prophase I. These targets include 435 protein-coding genes and 71 transposons that show an enrichment for carbohydrate biosynthetic and metabolic pathways. Our study provides strong evidence that 21-nt phasiRNAs act in a target-cleavage mode and may facilitate the progression of meiosis by fine-tuning carbohydrate biosynthesis and metabolism in male germ cells.
Greenhouse gas consequences of the China dual credit policy
Authors: He Xin , Ou Shiqi , Gan Yu , Lu Zifeng , Przesmitzki Steven Victor , Bouchard Jessey Lee , Sui Lang , Amer Amer Ahmad , Lin Zhenhong , Yu Rujie , Zhou Yan , Wang Michael 
Published: October 2020

AbstractFor over ten years, China has been the largest vehicle market in the world. In order to address energy security and air quality concerns, China issued the Dual Credit policy to improve vehicle efficiency and accelerate New Energy Vehicle adoption. In this paper, a market-penetration model is combined with a vehicle fleet model to assess implications on greenhouse gas (GHG) emissions and energy demand. Here we use this integrated modeling framework to study several scenarios, including hypothetical policy tweaks, oil price, battery cost and charging infrastructure for the Chinese passenger vehicle fleet. The model shows that the total GHGs of the Chinese passenger vehicle fleet are expected to peak in 2032 under the Dual Credit policy. A significant reduction in GHG emissions is possible if more efficient internal combustion engines continue to be part of the technology mix in the short term with more New Energy Vehicle penetration in the long term.
Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice
Authors: Sun Jiaqi , Huang Yinong , Gong Jin , Wang Jiancheng , Fan Yubao , Cai Jianye , Wang Yi , Qiu Yuan , Wei Yili , Xiong Chuanfeng , Chen Jierui , Wang Bin , Ma Yuanchen , Huang Lihua , Chen Xiaoyong , Zheng Shuwei , Huang Weijun , Ke Qiong , Wang Tao , Li Xiaoping , Zhang Wei , Xiang Andy Peng , Li Weiqiang 
Published: October 2020

AbstractPericytes play essential roles in blood–brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRβ, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.
Experimental study on the mechanical properties of Guiyang red clay considering the meso micro damage mechanism and stress path
Authors: Zhang Yanzhao , Zuo Shuangying , Li Rita Yi Man , Mo Yunchuan , Yang Guosheng , Zhang Min 
Published: October 2020

AbstractThis study investigated the macroscopic physical and mechanical properties of Guiyang red clay during surcharge loading, lateral excavation and lateral unloading with axial loading, and clarified the failure mechanism of microstructure before and after shear under different stress paths of CTC, RTC and TC. Consolidated undrained triaxial shear permeability, SEM scanning, XRF fluorescence spectrum analysis and XRD diffraction tests were conducted to simulate the actual engineering conditions. The stress–strain curve, shear strength, pore water pressure variation rule and macroscopic failure mode of soil samples under different stress paths were analysed. In addition, Image Pro Plus 6.0 and PCAS were used to study the relationship between the macro mechanical properties and micro microstructure failure under different stress paths. The stress–strain curves from CTC, RTC and TC in CU tests were different, with the peak values of shear stress under the three stress paths being P-increasing, equal P-path and P-decreasing path. Moreover, the internal friction angle and cohesion of the increasing P path were higher than those of equal P path and decreasing P path, hence, the influence of stress paths on the cohesion is greater than that of internal friction angle. The pore water pressure is strongly dependent on the stress path, and the variation characteristics of pore water pressure are consistent with the change in the law of the stress–strain curve. Under the same confining pressure in the P-increasing path, the shear failure zone runs through the whole soil sample, and the shear failure zone is significant, whereas under the condition of the P-reducing path, the shear failure angle of soil sample is about 65°, 55° and 45°, and in the equal P path, the soil sample is dominated by the confining pressure, with no obvious microcrack on the surface of the soil sample. The difference is that the distribution of pores in the path of increasing P and equal P is directional, and the anisotropy rate is small, while the distribution of pores in soil samples with shear failure and before shear is random and the anisotropy rate is high.