bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lovastatin Inhibits EMT and Metastasis of Triple-Negative Breast Cancer Stem Cells Through Dysregulation of Cytoskeleton-Associated Proteins
Authors: Zheng Chanjuan , Yan Shichao , Lu Lu , Yao Hui , He Guangchun , Chen Sisi , Li Ying , Peng Xiaojun , Cheng Zhongyi , Wu Mi , Zhang Qiuting , Li Guifei , Fu Shujun , Deng Xiyun 
Published: January 2021

Abstract
Background

Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of breast cancer. Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal-like cells capable of migration, invasion, and metastasis. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, could inhibit stemness properties of cancer stem cells (CSCs) derived from TNBC cell in vitro and in vivo. This study is aimed at investigating whether lovastatin inhibits TNBC CSCs by inhibiting EMT and suppressing metastasis and the mechanism involved.
Methods

LC-MS/MS was used to identify differentially regulated lysine acylation between TNBC and non-TNBC CSCs. In vivo, two nude mouse models were used to study the tumor growth, EMT phenotype, and metastasis of breast CSCs. The effect of lovastatin on EMT-related proteins was examined by immunohistochemistry, western blot and immunofluorescence-confocal microscopy. TGF-β1-challenged immortalized mammary epithelial cells MCF10A were treated with lovastatin and the change of cell morphology were detected by microscopic examination. Cell migration was detected by wound-healing assay. The formation of pseudopodia and the distribution of F-actin were investigated by transmission electron microscopy (TEM) and immunofluorescence-confocal microscopy, respectively. Bioinformatics analysis was used to evaluate the correlation between the expression of cytoskeleton-associated genes and overall survival of breast cancer patients.
Results

Lovastatin dysregulated lysine succinylation of cytoskeleton-associated proteins in CSCs derived from TNBC MDA-MB-231 cell. Lovastatin inhibited EMT as demonstrated by down-regulation of the protein levels of Vimentin and Twist in MDA-MB-231 CSCs in vitro and vivo and by reversal of TGF-β1-induced morphological change in MCF10A cells. Combination of lovastatin with doxorubicin synergistically inhibited liver metastasis of MDA-MB-231 CSCs. Lovastatin also inhibited the migration of MDA-MB-231 CSCs. The disruption of cytoskeleton in TNBC CSCs by lovastatin was demonstrated by the reduction of the number of pseudopodia and the relocation of F-actin cytoskeleton. Bioinformatics analysis revealed that higher expression levels of cytoskeleton-associated genes were characteristic of TNBC and predicted poorer overall survival in breast cancer patients.
Conclusions

Lovastatin could inhibit the EMT and metastasis of TNBC CSCs in vitro and in vivo through dysregulation of cytoskeleton-associated proteins.
PNO1 promotes human cholangiocarcinoma tumorigenesis and chemosensitivity
Authors: Chen Chuang , Huang Shan , Wu Guobin , Wang Zongyu , Lin Dongyi , He Jianbo , Li Kezhi , Han Zhiwei , Chen Xinxin , Qiu Wenxia , Wang Yu , Zhao Shulei , Gong Wei , Xu Shifeng 
Published: January 2021

Abstract
Background

The partner of NOB1 homolog (PNO1) is important for ribosome biogenesis and serves as an oncogene in several cancers. However, the role of PNO1 in cholangiocarcinoma (CHOL) remains largely unknown.
Methods

The method of mRNA microarray analysis, high-throughput screening technologies, on-line databases analysis, PDXs models, biochemistry and molecular biology have been utilized to reveal the role of PNO1 in the progression of CHOL.
Results

PNO1 was significantly upregulated in CHOL tissues and predicted poor prognosis. PNO1 could induce cell proliferation and metastasis in vitro and in vivo. In CHOL cells expressing wild-type p53, PNO1 knockdown increased expression of p53 and its downstream gene p21 and decreased cell viability; these effects were blocked by p53 knockout and attenuated by the p53 inhibitor PFT-a. Furthermore, PNO1 knockdown reduced global protein synthesis and inhibiting MDM2-mediated ubiquitination and p53 degradation. Moreover, PNO1 overexpression enhanced the sensitivity to bortezomib treatment in CHOL. In addition, MYC overexpression promoted PNO1 promoter activity while MYC knockdown decreased PNO1 mRNA and protein, which led to decreased cell viability and clone formation. The expression of MYC was found positively correlated with PNO1 in CHOL patients.
Conclusions

Collectively, upregulation of PNO1 by MYC promotes cholangiocarcinoma tumorigenesis through suppressing p53 signaling pathway and enhanced the sensitivity to bortezomib treatment. PNO1 serves as a candidate of therapeutic target in CHOL treatment and clinical chemotherapy regimen.
A combined Globo H-OCT4-T7 immunotherapy restrains colorectal tumor growth
Authors: Xu Jiangyao , Liu Maixian , Liu Shikang , Liu Kan , Ouyang Zijun , Jin Guangyi , Lu Desheng , Jiang Wenxiao , Shu Xingsheng , Xu Gaixia , Li Yang , Wu Christina C. N. , Chen Meiyi , Lin Guimiao , Wang Xiaomei 
Published: January 2021

Abstract
Background: Malignant tumors express multiple common markers that might constitute targets for tumor immunotherapy. Methods: Here we performed antigen epitope screening and molecular docking to design a new combination vaccine based on covalently linking Globo H and Oct 4 with a TLR7 agonist. We mainly use flow cytometry to analyze the changes in lymphocyte differentiation after the vaccine is applied. Use Elisa technology to detect the antibodies produced by the vaccine and the changes in lymphokines. In order to supplement the immunological data, RNA sequencing was performed on untreated and vaccine-treated tumors to define the interference of the vaccine on the genome-wide gene expression profile.Results: Our results demonstrated that the Globo H-OCT4-T7 conjugate vaccine effectively induced cellular uptake, maturation and antigen presentation of BMDCs. The combination vaccine enhanced cytokine production, CTLs activity elicited high levels of IgG. Importantly, the tumor immune microenvironment was significantly improved in tumor-bearing mice treated by Globo H-OCT4-T7 conjugate vaccine, demonstrated by increased the ratio of M1 to M2 TAMs, reduced number of Tregs in PBMCs and promoted the infiltration of tumor-specific IFN γ-producing CD8+ T cells. Prophylactic vaccination of Globo H-OCT4-T7 significantly reduced tumor growth by >80 % in both CT26 transplanted mice and in a human PDX mouse model when exposing mice to the combined vaccine compared to control. Our novel, combination vaccine is safe and effective at preventing tumor growth in mice. Conclusions: This combination vaccine is more effective than the single vaccine, and thus has the potential to prevent OCT4 and Globo H from expressing cancer.
Genetic Characterization and Genome-Wide Association Mapping for Stem Rust Resistance in Spring Bread Wheat
Authors: Shewabez Elias , Bekele Endashaw , Alemu Admas , Mugnai Laura , Tadesse Wuletaw 
Published: January 2021

Abstract
Background Emerging wheat stem rust races has become a major threat to global wheat production. Finding additional loci responsible for resistance to these races and incorporating them into currently cultivated varieties is the most economical and environmentally sound strategy to combat this problem. Thus, this study aimed to characterize the genetic diversity of wheat and to identify the genetic loci conferring resistance to stem rust of wheat. To accomplish this study, 245 elite lines introduced from the International Center for Agricultural Research in the Dry Areas (ICARDA) were tested under natural stem rust pressure in the field at the Debre Zeit Agricultural Research Center, Ethiopia. The SNP marker data was retrieved from a 15K SNP wheat array. Association analysis was undertaken between SNP markers and best linear unbiased prediction (BLUP) value of the stem rust coefficient of infection (CI) using a mixed linear model. Results Phenotypic analysis revealed 46% of lines had a coefficient of infection (CI) between 0 to 19. An average 0.38 in Nei’s gene diversity, 0.20 in polymorphism information content, and 0.71 in major allele frequency of the whole genome were identified.A total of 46 marker-trait associations (MTAs) that were encompassed within 13 quantitative trait loci (QTL) on chromosomes 1B, 3A, 3B, 4A, 4B, and 5A were found for CI. Four major QTLs with –log10 (p) ≥ 3 (EWYP1B.1, EWYP1B.3, EWYP1B.4, and EWYP1B.5) were identified on chromosome 1B. Conclusions This study contributes several novel markers associated with stem rust resistance. These can be further facilitating durable rust resistance development through marker-assisted selection. The resistant wheat genotypes identified in this study are recommended to be used in the national wheat breeding programs to improve stem rust resistance. Key words: markers; Puccinia graminis f. sp. tritici; QTL
Polymorphisms and Gene-Gene Interaction in AGER/IL6 Pathway are Associated with Diabetic Ischemic Heart Disease
Authors: Liu Kuo , Xie Yunyi , Zhao Qian , Peng Wenjuan , Guo Chunyue , Zhang Jie , Zhang Ling 
Published: January 2021

Abstract
Background: The aim of the present study is to demonstrate the association of AGER and IL6R gene polymorphisms with diabetic ischemic heart disease (IHD), and to investigate the effect of gene-gene interaction on disease risk. Methods: Our study included 204 ischemic heart disease cases who have previously been diagnosed as diabetes before the diagnoses of IHD, and 882 health controls. Polygenic risk score (PRS) was calculated by summing the number of risk alleles of all the candidate single nucleotide polymorphisms (SNPs). Logistic regression was used to find the association of candidate SNPs and PRS with diabetic ischemic heart disease. Generalized multifactor dimensionality reduction (GMDR) was used to illustrate gene-gene interaction. Haplotypes were identified and analyzed via Haploview and Plink software. Results: The rs184003 and rs2070600 in AGER gene were significantly associated with the risk of diabetic ischemic heart disease (Padditive=0.005; Padditive=0.025, respectively). For IL6R rs4845625, CT and TT genotype were associated with lower risk of the disease comparing with CC genotype (OR=0.692, P=0.045; OR=0.503, P=0.003, respectively). After adjustment for covariates, the association of rs4845625 with disease remained statistically significant. Haplotypes in AGER gene (rs184003-rs1035798-rs2070600-rs1800624) and IL6R gene (rs7529229-rs4845625-rs4129267-rs7514452-rs4072391) were both significantly associated with diabetic ischemic heart disease (P=0.008; P=0.007). PRS was associated with the disease (OR=1.106, P=0.020) after adjusting for covariates. The GMDR analysis suggested that rs184003 and rs4845625 was the best interaction model after permutation testing (P=0.001) with a cross-validation consistency of 10/10. Conclusions: SNPs and haplotypes in AGER and IL6R gene and the interaction of rs184003 in AGER with rs4845625 in IL6R were significantly associated with diabetic ischemic heart disease.
The Effectiveness of Simulation-based Ultrasound-guided Regional Anesthesia Training Programs for Anesthesia Residents: a Prospective Randomized Controlled Trial
Authors: Lin Zeng-Mao , Kong Hao , Zhang Feng , Li Xue , Huang Da , Li Yu-Ting , Zhang Hong 
Published: January 2021

Abstract
BackgroundOptimizing educational programs for obtaining and maintaining competency in ultrasound-guided regional anesthesia (UGRA) is needed for anesthesia residents. This study aimed to assess the effectiveness of simulation-based training programs on the UGRA skills of senior anesthesia residents.MethodsThis prospective assessor-blind randomized controlled trial was conducted in a tertiary hospital in November 2019. Twenty anesthesia residents who had been in a clinical rotation in anesthesiology for 3-5 years were randomly allocated to either the workshop group (WG) or the control group (CG) for pretechnical procedure training on UGRA. Following didactic lectures for both groups, simulation-based workshops were performed only for the WG. All participating trainees were assessed by written examination, ultrasound scanning and anatomy recognition in live human models and ultrasound-guided target injections in porcine meat models. The written examination score, sonographic proficiency scores, time taken to perform the injections and errors were recorded and analyzed.ResultsThe simulation-based training program significantly reduced the time taken for target injections performed by trainees in the WG (183.9±44.8 seconds) compared with those in the CG (239.6±64.2 seconds): mean difference -55.8 (-107.7, -3.7), P=0.037. The error score was also significantly lower in the WG than in the CG. The sonographic proficiency scores of the thoracic paravertebral structures, brachial plexus and femoral nerve scanning were significantly higher for trainees in the WG than for those in the CG, as were the total scores for the four stations on live human models.ConclusionsFor senior anesthesia residents, the simulation-based training program can improve UGRA skills and might enhance clinical competence.Trial RegistrationChinese clinical trial registry, ChiCTR-IPR-1900027585, Principal investigator: Hong Zhang, Date of registration: November 19, 2019 URL: http://www.chictr.org.cn/
Distinct mutations and lineages of SARS-CoV-2 virus in the early phase of COVID-19 pandemic and subsequent global expansion
Authors: Chen Yan , Li Shiyong , Wu Wei , Geng Shuaipeng , Mao Mao 
Published: January 2021

Abstract
A novel coronavirus, SARS-CoV-2, has caused over 85 million cases and over 1.8 million deaths worldwide since it occurred twelve months ago in Wuhan, China. Here we conceptualized the time-series evolutionary and expansion dynamics of SARS-CoV-2 by taking a series of cross-sectional view of viral genomes from early outbreak in January in Wuhan to early phase of global ignition in early April, and finally to the subsequent global expansion by late December 2020. By scrutinizing cases from early outbreak, we found a viral genotype from the Seafood Market in Wuhan featured with two concurrent mutations has become the overwhelmingly dominant genotype (95.3%) of the pandemic. By analyzing 4,013 full-length SARS-CoV-2 genomes from different continents by early April, we were able to visualize the genomic diversity over a 14-week timespan since the outbreak in Wuhan. 2,954 unique nucleotide substitutions were identified with 31 of the 4,013 genomes remaining as ancestral type, and 952 (32.2%) mutations recurred in more than one genome. 11 major viral genotypes with unique geographic distributions were identified. As the pandemic has been unfolding for more than one year, we also used the same approach to analyze 261,323 full-length SARS-CoV-2 genomes from the world since the outbreak in Wuhan (i.e. including all the available viral genomes in the GISAID database as of 25 December 2020) in order to recapitulate our findings in a real-time fashion and to present a full catalogue of SARS-CoV-2 mutations. We demonstrated the viral genotypic dynamics from different geographic locations over one-year timespan reveal transmission routes and indicate subsequent expansion. This study, to our knowledge, is heretofore the largest and most comprehensive genomic study of SARS-CoV-2. It indicates the viral genotypes can be utilized as molecular barcodes in combination with epidemiologic data to monitor the spreading routes of the pandemic and evaluate the effectiveness of control measures. Moreover, the dynamics of viral mutational spectrum in the study may help the early identification of new strains in patients to reduce further spread of infection, and guide the development of molecular diagnosis and vaccines against COVID-19, and last but not the least help assess their accuracy and efficacy.
Bird’s-Eye View Provided in Real-time via Drone Improves Spatial Perception for Team Sports
Authors: Miura Satoshi , Nakagawa Kento , Hirooka Kazumasa , Matsumoto Yuya , Umesawa Yumi , Fujimoto Hiroshi , Kanosue Kazuyuki , Fujie Masakatsu 
Published: January 2021

Abstract
Sports-assisting technologies have been developed; however, most are to improve performances in individual sports such as ski, batting, and swimming. Few studies focused on team sports which require not only motor ability of individual players but also perceptual abilities to grasp positions of their own and others. In the present study, we aim to validate the feasibility of a visual feedback system for the improvement of space perception in relation to other persons that is necessary. Herein, the visual feedback system is composed of a flying drone that transmits the image to the participant’s smart glasses. With and without the system, the participant was able to see his/her own relative position in real time though the glass. Nine participants tried to position themselves on the line between two experimenters 30 m away from each other, which simulated the situation of a baseball cutoff man. As a result, the error distance between the participants’ position and the line significantly decreased when using the system than that without the system. Furthermore, after participants practiced the task with the system the error decreased compared to that before the practice. In conclusion, the real-time feedback system from the bird’s-eye view would work for improving the accuracy of space perception.
An AXIN2 Mutation and Perinatal Risk Factors Contribute to Sagittal Craniosynostosis: Evidence From a Chinese Female Monochorionic Diamniotic Twin Family
Authors: Xu Jin , Yan Qing , Song Chengcheng , Liang Jingjia , Zhao Liang , Zhang Xin , Weng Zhenkun , Xu Cheng , Liu Qian , Xu Shuqin , Pang Lu , Zhang Liye , Wang Gang , Sun Yuan , Gu Aihua 
Published: January 2021

Abstract
Background: Craniosynostosis, defined as premature fusion of one or more cranial sutures, affects approximately 1 in every 2000-2500 live births. Sagittal craniosynostosis (CS), the most prevalent form of isolated craniosynostosis, is caused by interplay between genetic and perinatal environmental insults. However, the underlying details remain largely unknown. Methods: The proband (a female monochorionic twin diagnosed with CS), her healthy co-twin sister and parents were enrolled. Obstetric history was extracted from medical records. Genetic screening was performed by whole exome sequencing (WES) and confirmed by Sanger sequencing. Functional annotation, conservation and structural analysis were predicted in public database. Phenotype data of AXIN2 knockout mice was downloaded from The International Mouse Phenotyping Consortium (IMPC, http://www.mousephenotype.org).Results: Obstetric medical records showed that, except for the shared perinatal risk factors by the twins, the proband suffered additional persistent breech presentation and intrauterine growth restriction. We identified a heterozygous mutation of AXIN2 (c.1181G>A, p.R394H, rs200899695) in monochorionic twins and their father, but not in the mother. This mutation is not reported in Asian population and results in replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of AXIN2 protein, which is highly conserved across species. The mutation was predicted to be potentially deleterious by in silico analysis. Incomplete penetrance of AXIN2 haploinsufficiency was found in female mice.Conclusions: AXIN2 (c.1181G>A, p.R394H, rs200899695) mutation confers susceptibility and perinatal risk factors trigger the occurrence of sagittal craniosynostosis. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis in Chinese population.
Effect of Pathogenesis-Based Individualized Thrombectomy on Treatment Result and Prognosis of Acute Intracranial Large-Artery Occlusion Patients
Authors: Liu Yong-Chang , Zheng Ming-Ming , Li Yan , Xie Song-Wang , Liu Qing-Ran , Wang Jun-Yong 
Published: January 2021

Abstract
BackgroundTo explore the effect and prognosis of individualized thrombus removal methods based on different pathogenesis. Methods151 patients with acute cerebral infarction who were admitted to the hospital for intracranial artery interventional thrombus removal from January 2018 to November 2019 were selected as the research objects. Patients in the experimental group selected different thrombectomy methods based on medical history, pathogenesis, and cerebrovascular angiography results. Aspiration and embolization are the first choice for embolism, and stent embolization is the first choice for vascular stenosis. Compare the medical history, admission NHISS score, the time from the end of cerebral angiography to recanalization, the number of thrombus removal, MRS score at 3 months, complications, etc . ResultsThere was no statistical difference in the basic data of the three groups. The time from the end of angiography to recanalization in the control group was significantly longer than that in the experimental suction group. There was a statistical difference between the control group and the experimental stent group in one-time thrombus removal opening rate (P=0.048). The vascular recanalization rate was statistically different among the three groups (P=0.611). The good prognosis rates of the experimental stent group and the experimental suction group were higher than those of the control group. ConclusionThe first choice for patients with cerebral infarction caused by embolization can shorten the recanalization time. Stent removal is the first choice for patients with cerebral infarction caused by atherosclerosis, which can increase the opening rate of thrombus removal. Individualized selection of different thrombus removal methods based on the pathogenesis can improve the good prognosis rate of patients.
Antibiotic Allergy and Blood Eosinophils Percent Could Be Prognostic Indicators of Glioma
Authors: Cao Liming , Lv Zhanghua , Wang Weiliang , Li Xue , Shi Jing , Liang Hongsheng , Zhang Yiwei , Hu Fulan 
Published: January 2021

Abstract
Background: Antibiotic allergy and blood eosinophil percentage (EOS%) may play an important role in the prognosis of gliomas, but few studies reported the relationship between antibiotic allergy and glioma as well as EOS% and glioma. The aim of our study was to estimate the relationships between antibiotic allergy, blood eosinophil percentage (EOS%) and glioma prognosis and to conduct a nomogram model for glioma patients. Estimating the effect of antibiotic allergy and EOS% on glioma prognosis may conduce to finding low-cost and safe prognostic indicators of glioma.Methods: We conducted a retrospective cohort study with 656 glioma patients to estimate the associations between antibiotic allergy, EOS% and glioma prognosis by Kaplan-Meier and Cox regression analysis. Stratified analyses were performed according to tumor grade. We constructed a nomogram with age at diagnosis, gender, tumor grade, antibiotic allergy, EOS% to predict the survival probabilities of glioma. Results: During 12 months follow-up, a total of 227 patients were alive and 318 patients died. Antibiotic allergy and EOS% >1.65 conferred a survival advantage on glioma patients. In the stratified analysis by tumor grade, antibiotic allergy was significantly associated with the prognosis of the prognosis of low-grade gliomas (HR = 0.36, 95%CI: 0.13-0.97) and high-grade gliomas (HR = 0.58, 95%CI: 0.36-0.93) in the univariate Cox regression analysis. However, after adjusting for confounding factors in the multivariate Cox regression analysis, antibiotic allergy was only significantly associated with high-grade gliomas (HRadj = 0.50, 95%CI: 0.30-0.82); the relationship between EOS% and glioma prognosis was restricted to low-grade gliomas (HRadj = 0.50, 95%CI: 0.30-0.82). The C-index of nomogram was 0.74.Conclusions: Antibiotic allergy was a protective prognosis factor of high-grade gliomas, EOS% >1.65 was a protective prognosis factor of low-grade gliomas. The nomogram with antibiotic allergy and EOS% could effectively predict the survival probability of glioma.