bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis
Authors: Wu Binhua , Zhang Ligang , Yu Yunfei , Lu Tongyi , Zhang Yinmei , Zhu Wenhui , Song Qifang , Lv Chengding , Guo Jiaying , Tian Yiqiao , Deng Ning 
Published: May 2020

AbstractmiRNAs have emerged as a pivotal component of gene regulatory networks, mediating cytokines secretion, cell cycle, and differentiation regulation. However, how miRNAs collaborate with transcription factors and downstream effector proteins that determine the fate of ovarian cancer cells remains to be understood, especially regarding to mechanism of tumor angiogenesis regulation. Based on the qRT-PCR and IHC analysis, we found that miR-6086 was maintained a very low level both in ovarian cancer cell lines and tissues. Further, we identified OC2 and EGFL6 as the direct targets of miR-6086 by luciferase assay and we observed an inverse relationship between the expression of miR-6086 and the OC2/VEGFA/EGFL6 axis. The Western blotting analysis suggested that OC2 could directly upregulate VEGFA and indirectly up-regulate EGFL6 through VEGFA. Moreover, miR-6086 could indirectly downregulate VEGFA through OC2. In addition, miR-6086, siOC2 and siEGFL6 could negatively regulate the tumor growth and angiogenesis of ovarian cancer (Skov3) in the animal studies, with the inhibition rates of 77.07%, 69.89%, and 73.62%, respectively (**p < 0.01). Moreover, the tumor cell proliferation, migration, and invasion of ovarian cancer cell lines (Caov3 and Skov3) and vascular formation (HUVECs) were significantly suppressed in vitro, by decreasing the AKT/MAPK pathways (*p < 0.05). Taken together, our results reveal that miR-6086 can suppress the angiogenesis networks in ovarian cancer by down-regulating the OC2/VEGFA/EGFL6 axis, directly or indirectly, which may provide potential targets for tumor therapeutics.
FTSJ1 regulates tRNA 2ʹ-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression
Authors: He Qihan , Yang Lin , Gao Kaiping , Ding Peikun , Chen Qianqian , Xiong Juan , Yang Wenhan , Song Yi , Wang Liang , Wang Yejun , Ling Lijuan , Wu Weiming , Yan Jisong , Zou Peng , Chen Yuchen , Zhai Rihong 
Published: May 2020

AbstractNon-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The mechanisms underlying NSCLC tumorigenesis are incompletely understood. Transfer RNA (tRNA) modification is emerging as a novel regulatory mechanism for carcinogenesis. However, the role of tRNA modification in NSCLC remains obscure. In this study, HPLC/MS assay was used to quantify tRNA modification levels in NSCLC tissues and cells. tRNA-modifying enzyme genes were identified by comparative genomics and validated by qRT-PCR analysis. The biological functions of tRNA-modifying gene in NSCLC were investigated in vitro and in vivo. The mechanisms of tRNA-modifying gene in NSCLC were explored by RNA-seq, qRT-PCR, and rescue assays. The results showed that a total of 18 types of tRNA modifications and up to seven tRNA-modifying genes were significantly downregulated in NSCLC tumor tissues compared with that in normal tissues, with the 2ʹ-O-methyladenosine (Am) modification displaying the lowest level in tumor tissues. Loss- and gain-of-function assays revealed that the amount of Am in tRNAs was significantly associated with expression levels of FTSJ1, which was also downregulated in NSCLC tissues and cells. Upregulation of FTSJ1 inhibited proliferation, migration, and promoted apoptosis of NSCLC cells in vitro. Silencing of FTSJ1 resulted in the opposite effects. In vivo assay confirmed that overexpression of FTSJ1 significantly suppressed the growth of NSCLC cells. Mechanistically, overexpression of FTSJ1 led to a decreased expression of DRAM1. Whereas knockdown of FTSJ1 resulted in an increased expression of DRAM1. Furthermore, silencing of DRAM1 substantially augmented the antitumor effect of FTSJ1 on NSCLC cells. Our findings suggested an important mechanism of tRNA modifications in NSCLC and demonstrated novel roles of FTSJ1 as both tRNA Am modifier and tumor suppressor in NSCLC.
Transgelin is a poor prognostic factor associated with advanced colorectal cancer (CRC) stage promoting tumor growth and migration in a TGFβ-dependent manner
Authors: Elsafadi Mona , Manikandan Muthurangan , Almalki Sami , Mahmood Amer , Shinwari Tasneem , Vishnubalaji Radhakrishnan , Mobarak Mohammad , Alfayez Musaad , Aldahmash Abdullah , Kassem Moustapha , Alajez Nehad M. 
Published: May 2020

AbstractColorectal cancer (CRC) is the fourth most common cancer type globally. Investigating the signaling pathways that maintain cancer cell phenotype can identify new biomarkers for targeted therapy. Aberrant transforming growth factor-β (TGFβ) signaling has been implicated in CRC progression, however, the exact mechanism by which TGFβ exerts its function is still being unraveled. Herein, we investigated TAGLN expression, prognostic value, and its regulation by TGFβ in CRC. While TAGLN was generally found to be downregulated in CRC, elevated expression of TAGLN was associated with advanced CRC stage and predicted poor overall survival (hazard ratio (HR) = 1.8, log-rank testP-value = 0.014) and disease-free survival (HR = 1.6, log-rank testP-value = 0.046), hence implicating TAGLN as poor prognostic factor in CRC. Forced expression of TAGLN was associated with enhanced CRC cell proliferation, clonogenic growth, cell migration and in vivo tumor formation in immunocompromised mice, while targeted depletion of TAGLN exhibited opposing biological effects. Global gene expression profiling of TAGLN-overexpressing or TAGLN-deficient CRC cell lines revealed deregulation of multiple cancer-related genes and signaling pathways. Transmission electron microscopy (TEM) revealed ultrastructural changes due to loss of TAGLN, including disruption of actin cytoskeleton organization and aberrant actin filament distribution. Hierarchical clustering, principle component, and ingenuity pathway analyses revealed distinct molecular profile associated with TAGLNhighCRC patients with remarkable activation of a number of mechanistic networks, including SMARCA4, TGFβ1, and P38 MAPK. The P38 MAPK was the top predicted upstream regulator network promoting cell movement through regulation of several intermediate molecules, including TGFβ1. Concordantly, functional categories associated with cellular movement and angiogenesis were also enriched in TAGLNhighCRC, supporting a model for the molecular mechanisms linking TGFβ-induced upregulation of TAGLN and CRC tumor progression and suggesting TAGLN as potential prognostic marker associated with advanced CRC pathological stage.
Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer
Authors: Yang Jian , Gong Yuhua , Lam Vincent K. , Shi Yan , Guan Yanfang , Zhang Yanyan , Ji Liyan , Chen Yongsheng , Zhao Yongliang , Qian Feng , Chen Jun , Li Pingang , Zhang Fan , Wang Jiayin , Zhang Xuanping , Yang Ling , Kopetz Scott , Futreal P. Andrew , Zhang Jianjun , Yi Xin , Xia Xuefeng , Yu Peiwu 
Published: May 2020

AbstractIdentifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29, p < 0.0001 and HR = 7.664, 95% CI, 2.916–21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.
The therapeutic potential of mesenchymal stem cells for cardiovascular diseases
Authors: Guo Yajun , Yu Yunsheng , Hu Shijun , Chen Yueqiu , Shen Zhenya 
Published: May 2020

AbstractMesenchymal stem cells (MSCs) are derived from a wide range of sources and easily isolated and cultured. MSCs have the capacity for in vitro amplification and self-renewal, low immunogenicity and immunomodulatory properties, and under certain conditions, MSCs can be differentiated into a variety of cells. In the cardiovascular system, MSCs can protect the myocardium by reducing the level of inflammation, promoting the differentiation of myocardial cells around infarct areas and angiogenesis, increasing apoptosis resistance, and inhibiting fibrosis, which are ideal qualities for cardiovascular repair. Preclinical studies have shown that MSCs can be transplanted and improve cardiac repair, but challenges, such as their low rate of migration to the ischemic myocardium, low tissue retention, and low survival rate after transplantation, remain. This article reviews the potential and methods of MSC transplantation in the treatment of cardiovascular diseases (CVDs) and the challenges of the clinical use of MSCs.
Evidence for a three-dimensional quantum spin liquid in PbCuTe2O6
Authors: Chillal Shravani , Iqbal Yasir , Jeschke Harald O. , Rodriguez-Rivera Jose A. , Bewley Robert , Manuel Pascal , Khalyavin Dmitry , Steffens Paul , Thomale Ronny , Islam A. T. M. Nazmul , Reuther Johannes , Lake Bella 
Published: May 2020

AbstractThe quantum spin liquid is a highly entangled magnetic state characterized by the absence of static magnetism in its ground state. Instead, the spins fluctuate in a highly correlated way down to the lowest temperatures. Quantum spin liquids are very rare and are confined to a few specific cases where the interactions between the magnetic ions cannot be simultaneously satisfied (known as frustration). Lattices with magnetic ions in triangular or tetrahedral arrangements, which interact via isotropic antiferromagnetic interactions, can generate such a frustration. Three-dimensional isotropic spin liquids have mostly been sought in materials where the magnetic ions form pyrochlore or hyperkagome lattices. Here we present a three-dimensional lattice called the hyper-hyperkagome that enables spin liquid behaviour and manifests in the compound PbCuTe2O6. Using a combination of experiment and theory, we show that this system exhibits signs of being a quantum spin liquid with no detectable static magnetism together with the presence of diffuse continua in the magnetic spectrum suggestive of fractional spinon excitations.
Probing the energy conversion process in piezoelectric-driven electrochemical self-charging supercapacitor power cell using piezoelectrochemical spectroscopy
Authors: Krishnamoorthy Karthikeyan , Pazhamalai Parthiban , Mariappan Vimal Kumar , Nardekar Swapnil Shital , Sahoo Surjit , Kim Sang-Jae 
Published: May 2020

AbstractThe design and development of self-charging supercapacitor power cells are rapidly gaining interest due to their ability to convert and store energy in an integrated device. Here, we have demonstrated the fabrication of a self-charging supercapacitor using siloxene sheets as electrodes and siloxene-based polymeric piezofiber separator immobilized with an ionogel electrolyte. The self-charging properties of the fabricated device subjected to various levels of compressive forces showed their ability to self-charge up to a maximum of 207 mV. The mechanism of self-charging process in the fabricated device is discussed via “piezoelectrochemical effect” with the aid of piezoelectrochemical spectroscopy measurements. These studies revealed the direct evidence of the piezoelectrochemical phenomenon involved in the energy conversion and storage process in the fabricated device. This study can provide insight towards understanding the energy conversion process in self-charging supercapacitors, which is of significance considering the state of the art of piezoelectric driven self-charging supercapacitors.
Control of electron-electron interaction in graphene by proximity screening
Authors: Kim M. , Xu S. G. , Berdyugin A. I. , Principi A. , Slizovskiy S. , Xin N. , Kumaravadivel P. , Kuang W. , Hamer M. , Krishna Kumar R. , Gorbachev R. V. , Watanabe K. , Taniguchi T. , Grigorieva I. V. , Fal’ko V. I. , Polini M. , Geim A. K. 
Published: May 2020

AbstractElectron-electron interactions play a critical role in many condensed matter phenomena, and it is tempting to find a way to control them by changing the interactions’ strength. One possible approach is to place a studied system in proximity of a metal, which induces additional screening and hence suppresses electron interactions. Here, using devices with atomically-thin gate dielectrics and atomically-flat metallic gates, we measure the electron-electron scattering length in graphene and report qualitative deviations from the standard behavior. The changes induced by screening become important only at gate dielectric thicknesses of a few nm, much smaller than a typical separation between electrons. Our theoretical analysis agrees well with the scattering rates extracted from measurements of electron viscosity in monolayer graphene and of umklapp electron-electron scattering in graphene superlattices. The results provide a guidance for future attempts to achieve proximity screening of many-body phenomena in two-dimensional systems.
Protein-altering germline mutations implicate novel genes related to lung cancer development
Authors: Ji Xuemei , Mukherjee Semanti , Landi Maria Teresa , Bosse Yohan , Joubert Philippe , Zhu Dakai , Gorlov Ivan , Xiao Xiangjun , Han Younghun , Gorlova Olga , Hung Rayjean J. , Brhane Yonathan , Carreras-Torres Robert , Christiani David C. , Caporaso Neil , Johansson Mattias , Liu Geoffrey , Bojesen Stig E. , Le Marchand Loic , Albanes Demetrios , Bickeböller Heike , Aldrich Melinda C. , Bush William S. , Tardon Adonina , Rennert Gad , Chen Chu , Byun Jinyoung , Dragnev Konstantin H. , Field John K. , Kiemeney Lambertus FA. , Lazarus Philip , Zienolddiny Shan , Lam Stephen , Schabath Matthew B. , Andrew Angeline S. , Bertazzi Pier A. , Pesatori Angela C. , Diao Nancy , Su Li , Song Lei , Zhang Ruyang , Leighl Natasha , Johansen Jakob S. , Mellemgaard Anders , Saliba Walid , Haiman Christopher , Wilkens Lynne , Fernandez-Somoano Ana , Fernandez-Tardon Guillermo , Heijden Erik H. F. M. van der , Kim Jin Hee , Davies Michael P. A. , Marcus Michael W. , Brunnström Hans , Manjer Jonas , Melander Olle , Muller David C. , Overvad Kim , Trichopoulou Antonia , Tumino Rosario , Goodman Gary E. , Cox Angela , Taylor Fiona , Woll Penella , Wichmann Erich , Muley Thomas , Risch Angela , Rosenberger Albert , Grankvist Kjell , Johansson Mikael , Shepherd Frances , Tsao Ming-Sound , Arnold Susanne M. , Haura Eric B. , Bolca Ciprian , Holcatova Ivana , Janout Vladimir , Kontic Milica , Lissowska Jolanta , Mukeria Anush , Ognjanovic Simona , Orlowski Tadeusz M. , Scelo Ghislaine , Swiatkowska Beata , Zaridze David , Bakke Per , Skaug Vidar , Butler Lesley M. , Offit Kenneth , Srinivasan Preethi , Bandlamudi Chaitanya , Hellmann Matthew D. , Solit David B. , Robson Mark E. , Rudin Charles M. , Stadler Zsofia K. , Taylor Barry S. , Berger Michael F. , Houlston Richard , McLaughlin John , Stevens Victoria , Nickle David C. , Obeidat Ma’en , Timens Wim , Artigas María Soler , Shete Sanjay , Brenner Hermann , Chanock Stephen , Brennan Paul , McKay James D. , Amos Christopher I. 
Published: May 2020

AbstractFew germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.
Chaos-assisted two-octave-spanning microcombs
Authors: Chen Hao-Jing , Ji Qing-Xin , Wang Heming , Yang Qi-Fan , Cao Qi-Tao , Gong Qihuang , Yi Xu , Xiao Yun-Feng 
Published: May 2020

AbstractSince its invention, optical frequency comb has revolutionized a broad range of subjects from metrology to spectroscopy. The recent development of microresonator-based frequency combs (microcombs) provides a unique pathway to create frequency comb systems on a chip. Indeed, microcomb-based spectroscopy, ranging, optical synthesizer, telecommunications and astronomical calibrations have been reported recently. Critical to many of the integrated comb systems is the broad coverage of comb spectra. Here, microcombs of more than two-octave span (450 nm to 2,008 nm) is demonstrated through χ(2) and χ(3) nonlinearities in a deformed silica microcavity. The deformation lifts the circular symmetry and creates chaotic tunneling channels that enable broadband collection of intracavity emission with a single waveguide. Our demonstration introduces a new degree of freedom, cavity deformation, to the microcomb studies, and our microcomb spectral range is useful for applications in optical clock, astronomical calibration and biological imaging.
Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line
Authors: Su Yapeng , Ko Melissa E. , Cheng Hanjun , Zhu Ronghui , Xue Min , Wang Jessica , Lee Jihoon W. , Frankiw Luke , Xu Alexander , Wong Stephanie , Robert Lidia , Takata Kaitlyn , Yuan Dan , Lu Yue , Huang Sui , Ribas Antoni , Levine Raphael , Nolan Garry P. , Wei Wei , Plevritis Sylvia K. , Li Guideng , Baltimore David , Heath James R. 
Published: May 2020

AbstractThe determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigenetic responses of diseased cells upon drugging. We integrate experiments and theory to determine the trajectories that single BRAFV600E mutant melanoma cancer cells take between drug-naive and drug-tolerant states. Although single-cell omics tools can yield snapshots of the cell-state landscape, the determination of individual cell trajectories through that space can be confounded by stochastic cell-state switching. We assayed for a panel of signaling, phenotypic, and metabolic regulators at points across 5 days of drug treatment to uncover a cell-state landscape with two paths connecting drug-naive and drug-tolerant states. The trajectory a given cell takes depends upon the drug-naive level of a lineage-restricted transcription factor. Each trajectory exhibits unique druggable susceptibilities, thus updating the paradigm of adaptive resistance development in an isogenic cell population.
A deubiquitylase with an unusually high-affinity ubiquitin-binding domain from the scrub typhus pathogen Orientia tsutsugamushi
Authors: Berk Jason M. , Lim Christopher , Ronau Judith A. , Chaudhuri Apala , Chen Hongli , Beckmann John F. , Loria J. Patrick , Xiong Yong , Hochstrasser Mark 
Published: May 2020

AbstractUbiquitin mediated signaling contributes critically to host cell defenses during pathogen infection. Many pathogens manipulate the ubiquitin system to evade these defenses. Here we characterize a likely effector protein bearing a deubiquitylase (DUB) domain from the obligate intracellular bacterium Orientia tsutsugamushi, the causative agent of scrub typhus. The Ulp1-like DUB prefers ubiquitin substrates over ubiquitin-like proteins and efficiently cleaves polyubiquitin chains of three or more ubiquitins. The co-crystal structure of the DUB (OtDUB) domain with ubiquitin revealed three bound ubiquitins: one engages the S1 site, the second binds an S2 site contributing to chain specificity and the third binds a unique ubiquitin-binding domain (UBD). The UBD modulates OtDUB activity, undergoes a pronounced structural transition upon binding ubiquitin, and binds monoubiquitin with an unprecedented ~5 nM dissociation constant. The characterization and high-resolution structure determination of this enzyme should aid in its development as a drug target to counter Orientia infections.
A mechanistic account of serotonin’s impact on mood
Authors: Michely Jochen , Eldar Eran , Martin Ingrid M. , Dolan Raymond J. 
Published: May 2020

AbstractSelective serotonin reuptake inhibitors (SSRIs) constitute a first-line antidepressant intervention, though the precise cognitive and computational mechanisms that explain treatment response remain elusive. Using week-long SSRI treatment in healthy volunteer participants, we show serotonin enhances the impact of experimentally induced positive affect on learning of novel, and reconsolidation of previously learned, reward associations. Computational modelling indicated these effects are best accounted for by a boost in subjective reward perception during learning, following a positive, but not negative, mood induction. Thus, instead of influencing affect or reward sensitivity directly, SSRIs might amplify an interaction between the two, giving rise to a delayed mood response. We suggest this modulation of affect-learning dynamics may explain the evolution of a gradual mood improvement seen with these agents and provides a novel candidate mechanism for the unfolding of serotonin’s antidepressant effects over time.