bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the arcuate and middle longitudinal fasciculi in speech perception in noise in adulthood
Authors: Tremblay Pascale , Perron Maxime , Deschamps Isabelle , Kennedy‐Higgins Dan , Houde Jean‐Christophe , Dick Anthony Steven , Descoteaux Maxime 
Published: September 2018

AbstractIn this article, we used High Angular Resolution Diffusion Imaging (HARDI) with advanced anatomically constrained particle filtering tractography to investigate the role of the arcuate fasciculus (AF) and the middle longitudinal fasciculus (MdLF) in speech perception in noise in younger and older adults. Fourteen young and 15 elderly adults completed a syllable discrimination task in the presence of broadband masking noise. Mediation analyses revealed few effects of age on white matter (WM) in these fascicles but broad effects of WM on speech perception, independently of age, especially in terms of sensitivity and criterion (response bias), after controlling for individual differences in hearing sensitivity and head size. Indirect (mediated) effects of age on speech perception through WM microstructure were also found, after controlling for individual differences in hearing sensitivity and head size, with AF microstructure related to sensitivity, response bias and phonological priming, and MdLF microstructure more strongly related to response bias. These findings suggest that pathways of the perisylvian region contribute to speech processing abilities, with relatively distinct contributions for the AF (sensitivity) and MdLF (response bias), indicative of a complex contribution of both phonological and cognitive processes to age‐related speech perception decline. These results provide new and important insights into the roles of these pathways as well as the factors that may contribute to elderly speech perception deficits. They also highlight the need for a greater focus to be placed on studying the role of WM microstructure to understand cognitive aging.
Isotopic response of run‐off to forest disturbance in small mountain catchments
Authors: Vystavna Yuliya , Holko Ladislav , Hejzlar Josef , Perșoiu Aurel , Graham Neil D. , Juras Roman , Huneau Frederic , Gibson John 
Published: September 2018

AbstractStable water isotopes were applied to trace hydrological processes in an undisturbed (mature spruce forest) and a nearby disturbed (deforested from a bark beetle outbreak) lake catchments in the Czech Republic. Both catchments are situated above 1,000 m a.s.l. within the Šumava National Park and have similar environmental conditions. The isotopic compositions of precipitation, creeks, springs, and lakes were sampled at 3‐week intervals over one hydrological year. Water inputs to catchments were derived from isotopically similar local precipitation, whereas run‐off was found to have different isotopic signatures. Creeks in the undisturbed catchment had ~1‰ and ~7‰ higher δ18O and δ2H with ~2‰ lower d‐excess than in the disturbed catchment. The d‐excess in creeks of the undisturbed catchment was more pronounced, particularly during snowmelt, and highly heterogeneous as compared with the disturbed catchment. Creeks in the undisturbed catchment were mainly fed by precipitation during the warm period (May–October), whereas creeks in the disturbed catchment were mostly fed by precipitation during the cold period (November–April). Estimated mean transit times of creeks and springs were ~6 months, except for two creeks in the undisturbed catchment, which had residence times of ~1 year. Although evaporation and transpiration fluxes were apparently reduced in the disturbed catchment, transpiration ratios were similar for both catchments. The difference in isotope signatures between catchments was attributed to the altered role of the forest canopy in temporal water distribution, which produced changes in the water cycle, potentially influencing important biogeochemical processes.
Knockdown of USP28 enhances the radiosensitivity of esophageal cancer cells via the c‐Myc/hypoxia‐inducible factor‐1 alpha pathway
Authors: Weili Zhang , Zhikun Liu , Jianmin Wang , Qingbao Tian 
Published: September 2018

AbstractAcquired radioresistance is a major clinical obstacle in the treatment of esophageal cancer (EC). Ubiquitin‐specific protease 28 (USP28) has been implicated in tumor growth in various cancer types. However, the role of USP28 and its underlying mechanisms of radioresistance in EC remain unknown. In the current study, we found that USP28 and c‐Myc levels were upregulated in EC tissues and EC cell lines. The mRNA expression levels of USP28 and c‐Myc were increased in the radioresistant human EC cell line (ECA109R) compared with those in ECA109 cells. In addition, the expression levels of USP28 and c‐Myc were increased with increase in culture time after irradiation. Meanwhile, overexpression of USP28 decreased the radiosensitivity of ECA109 cells. In contrast, USP28 knockdown enhanced the radiosensitivity of ECA109R cells. Moreover, USP28 positively regulated the protein level of c‐Myc, and c‐Myc negatively regulated the radiosensitivity of ECA109 and ECA109R cells. Furthermore, c‐Myc reversed the inhibitory effect of USP28 on the radiosensitivity of EC cells. Additionally, c‐Myc enhanced the accumulation of hypoxia‐inducible factor‐1 alpha (HIF‐1α) at the posttranscriptional level, and the reinforcing effect of c‐Myc silencing on the radiosensitivity of EC cells could be reversed by HIF‐1α overexpression. Besides, knockdown of USP28 blocked the effect of c‐Myc on activation of ataxia telangiectasia‐mutated/ataxia telangiectasia and Rad3‐related DNA damage checkpoint after irradiation. In conclusion, knockdown of USP28 enhanced the radiosensitivity of EC cells by destabilizing c‐Myc and enhancing the accumulation of HIF‐1α. Therefore, USP28 may serve as a novel therapeutic target to overcome EC radioresistance.
A novel seven‐lncRNA signature for prognosis prediction in hepatocellular carcinoma
Authors: Yan Junhao , Zhou Chao , Guo Kuiyuan , Li Qian , Wang Zheng 
Published: September 2018

AbstractLiver cancer is still one of the leading causes of cancer‐related death worldwide. This study is dedicated to developing a multi–long noncoding RNA (lncRNA) model for risk stratification and prognosis prediction on patients with hepatocellular carcinoma (HCC). We first downloaded lncRNA expression profiles and corresponding clinical information of patients with liver cancer from The Cancer Genome Atlas database. Differentially expressed (DE) lncRNAs between HCC samples and normal samples were identified. In total, 308 patients with HCC were randomly divided into a training group (n = 154) and a testing group (n = 154). Univariate Cox regression and least absolute shrinkage and selection operator Cox regression analyses were performed to select the best survival‐related candidates from these DE lncRNAs in the training set. Seven lncRNAs (AC009005.2, RP11‐363N22.3, RP11‐932O9.10, RP11‐572O6.1, RP11‐190C22.8, RP11‐388C12.8, and ZFPM2‐AS1) were finally identified and used to construct a seven‐lncRNA signature. The signature could classify patients into high‐risk and low‐risk groups with significantly different overall survival. The area under the curve of receiver operating characteristic curve for the signature to predict 5‐year survival reached more than 0.75. Besides, the prognostic value of the seven‐lncRNA signature was independent of conventional clinical factors. The predictive performance of the signature was further validated in the testing set and the whole set. Functional enrichment analysis indicated that the seven prognostic lncRNAs may be involved in several essential biological processes and pathways. The current study demonstrated the potential clinical implications of the seven‐lncRNA signature for survival prediction of patients with HCC.
Liver kinase B1 overexpression controls mycobacterial infection in macrophages via FOXO1/Wnt5a signaling
Authors: Cui Junwei , Li Mingying , Liu Weiguo , Zhang Bianfang , Sun Bing , Niu Wenyi , Wang Yongliang 
Published: September 2018

AbstractMycobacterium tuberculosis (Mtb) is a primary cause of tuberculosis (TB), which has infected more than one‐third of the world’s population. Mtb survival and subsequent inflammation in macrophages are important components of TB. Liver kinase B1 (LKB1) has demonstrated anti‐inflammation effects, but its function and underlying mechanism in mycobacteria‐infected macrophages remains unknown. In the current study, we discovered that LKB1 was markedly decreased in Mtb‐infected THP‐1 and U937 macrophages. Moreover, LKB1 overexpression inhibited Mtb survival in macrophages. Mtb infection increased expression of nitric oxide, inducible nitric oxide synthase, and inflammation‐related cytokines interleukin (IL)‐6, tumor necrosis factor‐α, and IL‐1β, whereas pcDNA3‐LKB1 transfection inhibited the release of these cytokines in THP‐1 and U937 cells. Furthermore, LKB1 overexpression significantly decreased protein expression of Wnt5a, which is dependent on the elevation of forkhead box protein O1 (FOXO1). Generally, we show that interruption of FOXO1 or overexpression of Wnt5a can reverse the effects of LKB1 on mycobacterial intracellular survival, nitric oxide, inducible nitric oxide synthase expression, and inflammatory cytokine release. These findings indicate important roles for LKB1, FOXO1, and Wnt5a in controlling mycobacteria and cell inflammation.
Retracted: KDM6B promotes ovarian cancer cell migration and invasion by induced transforming growth factor‐β1 expression
Authors: Liang Shumei , Yao Qingmin , Wei Deying , Liu Ming , Geng Feng , Wang Qin , Wang Yun‐shan 
Published: September 2018

AbstractKDM6B, also known as JMJD3, is a member of the family of histone lysine demethylase (KDMs), which is closely related to many types of cancers. However, its role and the underlying mechanisms in ovarian cancer remain unknown. Here we show that KDM6B is elevated in epithelial ovarian cancer and its expression level is closely related with metastasis and invasion. In addition, survival analysis showed that high expression of KDM6B was associated with low overall survival in ovarian cancer patients. Overexpression of KDM6B in epithelial ovarian cancer cells promoted proliferation, epithelial‐mesenchymal transition (EMT), migration and invasion in vitro, and enhanced metastatic capacities in vivo. On the contrary, silencing KDM6B in invasive and metastatic ovarian cancer cells inhibited these processes. Mechanistically, we found that KDM6B exerts its function by modulating the transforming growth factor‐β1 (TGF‐β1) expression, and TGF‐β1 signal pathway inhibitor LY2157299 significantly inhibited KDM6B‐induced proliferation, migration, metastasis, and EMT in ovarian cancer cells. Our findings, for the first time, reveal the pivotal role of KDM6B in the invasion and metastatic behavior of epithelial ovarian cancer. Thus, targeting KDM6B may be a useful strategy to interfere with these behaviors of epithelial ovarian cancer.
MiR‐490‐5p inhibits the stemness of hepatocellular carcinoma cells by targeting ECT2
Authors: Yu Yuanjie , Cai Ou , Wu Pengbo , Tan Shiyun 
Published: September 2018

AbstractTo explore the targeting relationship between miR‐490‐5p and ECT2 in hepatocellular carcinoma (HCC) and the influences of miR‐490‐5p and
ECT2 on the stemness of HCC cells. The expressions of miR‐490‐5p and
ECT2 in HCC tissues and adjacent tissues were identified by quantitative real‐time polymerase chain reaction (qRT‐PCR). The relationships between the expression levels of miR‐490‐5p/
ECT2 and the overall/disease‐free survival (OS/DFS) of patients with HCC were evaluated using correlative curves. In addition, the targeting relationship between miR‐490‐5p and
ECT2 was predicted by TargetScan and verified by dual‐luciferase reporter assay. Plasmid transfection was used for overexpression of
ECT2 in HepG2 cells, and transfection efficiency was verified by qRT‐PCR. Cell Counting Kit‐8 assay and cell sphere‐formation assay were conducted to detect the proliferation and sphere‐formation ability of HCC cells, respectively. Cell populations with different cell transfections were sorted using flow cytometry. The expression levels of proteins in the stem cell signaling pathway were determined using Western blot analysis. MiR‐490‐5p was remarkably downregulated, yet
ECT2 was upregulated in HCC tissues compared with adjacent tissues. MiR‐490‐5p expression was positively correlated with OS and DFS of patients with HCC, which were otherwise negatively correlated with
ECT2 expression.
ECT2 was validated to be the downstream target of miR‐490‐5p. Overexpression of miR‐490‐5p restrained the sphere formation ability, stemness, and proliferation of HCC cells. MiR‐490‐5p repressed the stemness of HCC cells through inhibiting the expression of
ECT2. MiR‐490‐5p may be an underlying therapeutic target in HCC treatment.
A unified mitochondria mechanistic target of rapamycin acyl‐coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells
Authors: Wu Jiawen , Xiao Shengxiang , Ren Jianwen , Zhang Dingwei 
Published: September 2018

AbstractMetformin exhibits antiproliferative and proapoptotic effects in a variety of diseases, characterized by malignant and nonmalignant hyperplastic cells; however, the underlying molecular mechanism of metformin in psoriasis has not been elucidated. In the current study, we found that after metformin treatment the proliferation of human immortalized keratinocytes (HaCaT) was significantly inhibited, while cell apoptosis was increased in a dose‐dependent manner, accompanied with enhanced protein expression of acyl‐coenzyme A dehydrogenase 10 (ACAD10). Furthermore, mechanism analysis revealed that ACAD10 expression is induced by downregulated activities of mechanistic target of rapamycin 1 (mTORC1) signaling rather than AMP‐activated protein kinase signaling. The inactivation of mTORC1 by rapamycin pretreatment or rotenone‐induced mitochondrial complex inhibition showed a similar effect because of the metformin treatment on the proliferation and apoptosis of HaCaT keratinocytes. Overexpression of mTORC1 almost reversed the antiproliferation and proapoptosis effects induced by metformin. This study showed that the metformin treatment inhibited HaCaT cells proliferation and promoted apoptosis by affecting the mitochondrial‐mTORC1 signaling and elevated the ACAD10 expression. Hence, metformin can be used as a potential therapeutic agent for psoriasis.
miR‐214‐5p targets KLF5 and suppresses proliferation of human hepatocellular carcinoma cells
Authors: Pang Jinzhong , Li Zheng , Wang Guangjun , Li Ningbo , Gao Yan , Wang Shuhui 
Published: September 2018

AbstractMicroRNAs (miRNAs) are small endogenous conserved RNAs regulating genes expression through base pairing with the 3′‐untranslated region (3′‐UTR) of target messenger RNAs. MiR‐214‐5p is a newly identified miRNA with its biological role largely unknown. In this study, we explored miR‐214‐5p expression status in 78 paired tumor and nontumor tissues obtained from patients with hepatocellular carcinoma (HCC) by RT‐qPCR. The effects of miR‐214‐5p expression on HCC cell proliferation, cell cycle progression, and cell migration were measured by CCK‐8 assay, flow cytometry, and wound‐healing assay. A dual‐luciferase activity assay was performed to identify whether KLF5 was a target of miR‐214‐5p. Kaplan‐Meier curve and log‐rank test were used to investigate the effects of miR‐214‐5p and KLF5 on overall survival and disease‐free survival of patients with HCC. We found miR‐214‐5p expression was sharply reduced in HCC tissues and cell lines compared with the normal tissues and cell lines. Functional assay revealed that miR‐214‐5p overexpression could downregulate cell proliferation, cell migration, and arrested cell cycle at G0/G1 phase. Further, we validated Krüppel‐like factor 5 (KLF5) as a direct target of miR‐214‐5p, and was upregulated in HCC and inversely correlated with the expression of miR‐214‐5p. Moreover, we found the low expression of miR‐214‐5p and high expression of KLF5 were correlated with tumor size, tumor stage, and poorer 5‐year overall survival and disease‐free survival of patients with HCC. In conclusion, our results suggested miR‐214‐5p functions as a tumor suppressor through targeting KLF5 in HCC. Also, miR‐214‐5p and KLF5 were identified as potential prognostic markers and might be therapeutic targets in HCC.
Structural and energetic understanding of novel natural inhibitors of Mycobacterium tuberculosis malate synthase
Authors: Shukla Rohit , Shukla Harish , Tripathi Timir 
Published: September 2018

AbstractPersistent infection by Mycobacterium tuberculosis requires the glyoxylate shunt. This is a bypass to the tricarboxylic acid cycle in which isocitrate lyase (ICL) and malate synthase (MS) catalyze the net incorporation of carbon during mycobacterial growth on acetate or fatty acids as the primary carbon source. To identify a potential antitubercular compound, we performed a structure‐based screening of natural compounds from the ZINC database (n = 1 67 740) against the M tuberculosis MS (MtbMS) structure. The ligands were screened against MtbMS, and 354 ligands were found to have better docking score. These compounds were assessed for Lipinski and absorption, distribution, metabolism, excretion, and toxicity prediction where 15 compounds were found to fit well for redocking studies. After refinement by molecular docking and drug‐likeness analysis, four potential inhibitors (ZINC1483899, ZINC1754310, ZINC2269664, and ZINC15729522) were identified. These four ligands with phenyl‐diketo acid were further subjected to molecular dynamics simulation to compare the dynamics and stability of the protein structure after ligand binding. The binding energy analysis was calculated to determine the intermolecular interactions. Our results suggested that the four compounds had a binding free energy of −201.96, −242.02, −187.03, and −169.02 kJ·mol−1, for compounds with IDs ZINC1483899, ZINC1754310, ZINC2269664, and ZINC15729522, respectively. We concluded that two compounds (ZINC1483899 and ZINC1754310) displayed considerable structural and pharmacological properties and could be probable drug candidates to fight against M tuberculosis parasites.
Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation
Authors: Hirata Kensuke , Takakura Yuki , Shibazaki Misato , Morii Mariko , Honda Takuya , Oshima Motohiko , Aoyama Kazumasa , Iwama Atsushi , Nakayama Yuji , Takano Hiroyuki , Yamaguchi Naoto , Yamaguchi Noritaka 
Published: September 2018

AbstractTransforming growth factor‐β (TGF‐β) induces apoptosis of normal epithelial cells, such as mammary epithelium. Although breast cancer progression associates with acquisition of resistance to TGF‐β‐induced apoptosis, the molecular mechanisms underlying this resistance are largely unknown. Here, we show that forkhead box protein A1 (FOXA1), which is known as a pioneer transcription factor, suppresses TGF‐β‐induced apoptosis of estrogen receptor–positive breast cancer cells. FOXA1 is found to inhibit nuclear translocation of Smad3, a key transcription factor downstream of TGF‐β signaling, through suppression of the binding of Smad3 to the nuclear import receptor importin7. Furthermore, RNA sequencing analyses show that knockdown of FOXA1 upregulates Smad3‐mediated proapoptotic gene expression. These results demonstrate that FOXA1 as a potent survival factor that suppresses TGF‐β‐induced apoptosis by inhibiting Smad3 signaling in estrogen receptor–positive breast cancer cells. Thus, we provide evidence for the first time that FOXA1 localizing to the cytoplasm negatively regulates Smad3‐induced apoptosis in TGF‐β‐mediated signal transduction.
Daphnetin inhibits RANKL‐induced osteoclastogenesis in vitro
Authors: Liu Xifang , Gao Xiaohang , Liu Yuanxin , Liang Dongsheng , Fu Ting , Song Yixin , Zhao Congzhe , Dong Bo , Han Weihua 
Published: September 2018

AbstractOsteoporosis is a common orthopedic disease which is associated with hyper‐activated osteoclastogenesis. Daphnetin is a natural coumarin derivative isolated from Genus Daphne, which possesses antiarthritis effect. However, the role of daphnetin in osteoclastogenesis has not been illustrated. This study aimed to investigate the effects of daphnetin on receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis in vitro. Our results showed that the osteoclast formation was significantly suppressed by daphnetin treatment in bone marrow‐derived macrophages (BMMs), which was illustrated by reduced number of tartrate‐resistant acid phosphatase positive multinucleated osteoclasts and decreased expression levels of tumor necrosis factor receptor‐associated factors (TRAF6), c‐Fos, nuclear factor of activated T cells c1, and cathepsin K. RANKL caused significant induction effects in reactive oxygen species (ROS) generation and nicotinamide adenine dinucleotide phosphate oxidase activity, whereas the induction was dramatically reduced after pretreatment with daphnetin. In addition, daphnetin prevented the RANKL‐induced activation of NF‐κB and Akt/GSK‐3β pathways in BMMs. These findings indicated that daphnetin exhibited an inhibitory effect on RANKL‐induced osteoclastogenesis in vitro. The effect of daphnetin might be mediated by inhibiting ROS signal transduction, as well as preventing the activation of NF‐κB and Akt/GSK‐3β signaling pathways. These findings indicated that daphnetin might be considered as a new therapeutic approach for the osteoporosis treatment.
Coexpression network analysis identified Krüppel‐like factor 6 (KLF6) association with chemosensitivity in ovarian cancer
Authors: Chen Ying , Bi Fangfang , An Yuanyuan , Yang Qing 
Published: September 2018

AbstractAlthough most patients with ovarian cancer (OC) are initially sensitive to paclitaxel/carboplatin combination chemotherapy, eventually they develop resistance to chemotherapy drugs and experience disease relapse. OC is the most lethal gynecological malignancy, and the five‐year survival rate is extremely low. Thus, research on specific biomarkers and potential targets for chemotherapy‐resistant patients with OC is needed. In our study, genes in the top 10% of variance in data set GSE30161 from chemoresistant and chemosensitive OC tissues were determined to conduct a weighted gene coexpression network analysis (WGCNA). The magenta module was most strongly related to OC chemoresponse. Gene ontology enrichment analysis indicated that the function of the magenta module primarily focused on transcription regulation, cell cycle control, and apoptosis modulation. Integration of the WGCN with the protein‐protein interaction network identified five candidate genes. These five genes were verified using the GSE51373 test set, and Krüppel‐like factor 6 (
KLF6) was identified as tightly linked to OC chemosensitivity. The receiver operating characteristic (ROC) curve showed that
KLF6 differentiated chemoresistant from chemosensitive OC tissues. The Kaplan‐Meier online database indicated that high
KLF6 expression was associated with poor OC prognosis. Gene set enrichment analysis determined that the
KLF6 mechanism was potentially associated with cell cycle, mTOR, and DNA‐damage repair signaling pathways. In conclusion,
KLF6 was identified in association with OC chemoresistance, and the mechanism of
KLF6‐mediated chemoresistance may involve the cell cycle, mTOR, and DNA‐damage repair signaling pathways.