bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi
Authors: Suarez Carlos , Silva Marta G. , Bastos Reginaldo G. , Doggett J. Stone , Riscoe Michael K. , Pou Sovitj , Winter Rolf , Dodean Rozalia A. , Nilsen Aaron 
Published: August 2020

Abstract
Background: The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. Endochin-like quinolones (ELQ)-300 and ELQ-316 proved safe and efficacious against related apicomplexans, such as Plasmodium spp., and ELQ-316 was also effective against B. microti, without showing toxicity in mammals.Methods: Inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. Percentage of parasitized erythrocytes was measured by flow cytometry. Effect of the ELQ drugs on the viability of actively replicating horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by ELISA. Results: We calculated IC50 ranging from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 at 72 hr among all cultured parasites tested. None of the parasites tested were able to replicate in cultures in the presence of the ELQs-300 and ELQ-316 at IC100, which range from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 hours. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions: ELQ-300 and ELQ-316 have a significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.
First report on molecular identification of Eimeria sp. from captive forest musk deer
Authors: Ren Ziwei , Yu Dong , Zhao Wei , Luo Yan , Cheng Jianguo , Wang Yin , Yang Zexiao , Yao Xueping , Yang Wei , Wu Xi , Li Yimeng 
Published: August 2020

Abstract
Background: Forest musk deer (Moschus berezovskii) is a national first-level protected and endangered wild animals in China. The intestinal coccidiosis of captive forest musk deer is one of the most important diseases. However, few studies have been conducted to quantify Eimeria sp. infection and to identify its molecules. Thus, the objective of this study was to investigate the Eimeria sp. infection in the intestinal tract of forest musk deer in Sichuan and Shaanxi, China, and to identify the 18S rRNA gene fragment of Eimeria sp. , which provides scientific basic experimental data for the molecular epidemiological investigation and population genetic analysis of Eimeria sp. of captive forest musk deer in 7 regions.Methods: 328 faecal samples of forest musk deer were collected from 7 farms. The DNA of Eimeria sp. in the positive samples was extracted and used as template for nested PCR amplification. The 18S rRNA gene fragment was connected with the plasmid vector, and the products were introduced into Escherichia coli (DH5α). The culture bacterial solution was used as a PCR reaction template for identification.Results: In total, we collected 328 faecal samples from forest musk deer in Lixian (n=54), Maoxian (n=52), Ma’erkang (n=49), Dujiangyan (n=55), Hanyuan (n=41), Luding (n=36) and Weinan (n=41). 198 (60.37%) faecal samples were positive for Eimeria sp. We analyzed the 18S rRNA gene sequence of Eimeria sp, and determined 34 types with similarity of 90.5% ~ 100%. A phylogenetic tree constructed based on the 18S rRNA gene sequence of Eimeria sp., it was confirmed that Eimeria sp. parasitized in the intestinal tract of forest musk deer was closely related to Eimeria alabamensis from Bos taurus, Eimeria faurei from Ovis aries and Eimeria ahsata from Ovis aries.Conclusions: To our knowledge, this was the first molecular identification of Eimeria sp. in the intestinal tract of forest musk deer. The study suggested that Eimeria sp. parasitizes in the intestinal tract of forest musk deer, which is their carrier.
Fungal mycoflora dysbiosis in gastric cancer
Authors: Zhong Mengya , Xiong Yubo , Zhao Jiabao , Gao Zhi , Ma Jingsong , Wu Zhengxin , Hong Xuehui , Song Yongxi 
Published: August 2020

Abstract
Background: Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal mycobiome in GC.Results: We observed significant gastric fungal dysbiosis in GC. Principal component analysis revealed separate clusters for the GC and control groups, and Venn diagram analysis indicated that the GC group showed a lower OTU abundance than the control. At the genus level, the abundances of 15 fungal biomarkers distinguished the GC group from the control, of which Candida (p = 0.000246) and Alternaria (p = 0.00341) were enriched in GC, while Saitozyma (p = 0.002324) and Thermomyces (p = 0.009158) were decreased. Combining the results of Welch’s t test and Wilcoxon rank sum test, C. albicans was significantly elevated in GC. The species richness Krona pie chart further revealed that C. albicans occupied 22% and classified GC from the control with an area under the receiver operating curve (AUC) of 0.743. Random forest analysis also confirmed that C. albicans could serve as a biomarker with a certain degree of accuracy. Moreover, compared with that of the control, the alpha diversity index was significantly reduced in the GC group. The Jaccard distance index and the Bray abundance index of the PCoA clarified separate clusters between the GC and control groups at the species level (p = 0.00051). Adonis (PERMANOVA) analysis and ANOVA showed that there were significant differences in fungal structure among groups (p = 0.001). Finally, FUNGuild functional classification predicted that saprotrophs were the most abundant taxa in the GC group.Conclusions: This study revealed GC-associated mycobiome dysbiosis characterized by an altered fungal composition and ecology and demonstrated that C. albicans can be a fungal biomarker for GC. In addition, C. albicans may mediate GC by reducing the diversity and richness of fungi in the stomach, contributing to the pathogenesis of GC.
An Intronic Variant of CHD7 Identified in Autism Patients Interferes With Neuronal Differentiation and Development
Authors: Zhang Ran , He Hui , Yuan Bo , Wu Ziyan , Wang Xiuzhen , Du Yasong , Chen Yuejun , Qiu Zilong 
Published: August 2020

Abstract
Background: Genetic compositions play critical roles in pathogenesis of autism spectrum disorders (ASD). Inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants are difficult to address. Here, we identified a recurrent inherited intronic variant in the CHD7 gene among Chinese ASD cohort, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. Here, we use differentiated human embryonic stem cells to investigate whether the ASD-associated CHD7 intronic variant may affect neural development. Methods: 167 ASD probands and their parents performed whole-exome sequencing and a recurrent inherited intronic variant was selected for functional research. We established human embryonic stem cells carrying this intronic variant using CRISPR/Cas methods and differentiated to neural progenitor cells and neurons for analysis. Results: The level of CHD7 mRNA significantly decreased in cell lines carrying homozygous mutants compared to control. Upon differentiation towards the forebrain neuronal lineage, neural cells carrying the CHD7 intronic variant exhibited developmental delay in neuronal differentiation and maturation. Importantly, TBR1, a gene also implicated in ASD, significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations could be rescued by knocking down TBR1, indicating that TBR1 may be responsible for defects in CHD7-related disorders. Finally, the CHD7 intronic variant generates three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function manners in functional assays. Limitations: The probands with CHD7 intronic variant were heterozygous while both cell lines established were homozygous, so the phenotype of the disease could not be completely simulated. Conclusions: Our study provides the crucial evidences for supporting the notion that intronic variant site of CHD7 is a potentially autism susceptible site, shedding new light on identifying functions of intronic variants in autism genetic studies.
Clinicopathological factors affecting the effect of neoadjuvant chemotherapy in patients with gastric cancer
Authors: Jiang Lin , Ma Zhiqiang , Ye Xin , Kang Weiming , Yu Jianchun 
Published: August 2020

Abstract
Background: Neoadjuvant chemotherapy is an important part of the comprehensive treatment of advanced gastric cancer (GC). The effect of neoadjuvant chemotherapy plays a key role in the prognosis of GC patients. Pathological response can represent the effect of neoadjuvant chemotherapy. However, evidence focused on pathological response and associated clinicopathological factors in GC patients is quite little. In this retrospective study, the clinicopathological factors affecting the effect of neoadjuvant chemotherapy in GC patients were investigated, and suggestions were proposed to improve the effect of neoadjuvant chemotherapy on GC.Methods: Retrospective analysis was performed on GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to March 2019 at Peking Union Medical College Hospital. Relevant clinicopathological data was collected to analyze the factors influencing the effect of neoadjuvant chemotherapy. Chi-square test was used for univariate analysis. Logistic regression was used for multivariate analysis. Receiver operating characteristic curve (ROC) was used to determine the cut-off value of variables which significantly influenced the effect of neoadjuvant chemotherapy.Results: A total of 171 GC patients were included in the study. Analyses showed that patients <60 years old (OR=1.971[1.032-3.764], P=0.040), pathological type of poor differentiation or signet ring cell carcinoma (OR=2.449[1.172-5.119], P=0.017), and weight loss during neoadjuvant chemotherapy (OR=2.091[1.090-4.011], P=0.027) were independent risk factors for neoadjuvant chemotherapy effect. In ROC analysis of weight change and neoadjuvant chemotherapy effect, area under the curve (AUC) was 0.591(P=0.046) and cut-off value of weight change was -2.9%. Chi-square test showed patients without weight loss during neoadjuvant chemotherapy had a higher rate of oral nutritional supplement (ONS) than patients with weight loss (P=0.046).Conclusions: Patients <60 years old, pathological type of poor differentiation or signet ring cell carcinoma, and weight loss during neoadjuvant chemotherapy were independent risk factors for neoadjuvant chemotherapy effect in GC patients. Patients with weight loss >2.9% during neoadjuvant may have a worse chemotherapy effect. Timely nutritional support such as ONS to maintain patients’ body weight is crucial for improving the effect of neoadjuvant chemotherapy.
GLP-1 Vasodilatation in Humans With Coronary Artery Disease is Not Adenosine Mediated.
Authors: Aetesam-ur-Rahman Muhammad , Giblett Joel P. , Khialani Bharat , Kyranis Stephen , Clarke Sophie J. , Zhao Tian X. , Braganza Denise M. , Clarke Sarah C. , West Nick E. J. , Bennett Martin R. , Hoole Stephen P. 
Published: August 2020

Abstract
Background Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect.Methods We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n=10); Placebo, normal saline infusion (Group P) (n=11); GLP-1 + Theophylline infusion (Group GT)(n=10); and Theophylline infusion (Group T) (n=10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time – Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR). Results There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G -0.23s (0.27) vs. group GT -0.18s (0.37), p=0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04s (0.15), p=0.30. The resulting decrease in BMR observed in group G persisted in group GT: -20.83 mmHg.s (24.54 vs. -21.20mmHg.s (30.41), p=0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine -2.0 ng/ml (-117.1, 14.8) vs. -0.5 ng/ml (-19.6, 9.4); p=0.60.Conclusion The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation.Trial Registration The local research ethics committee approved the study: REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.
MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis by Targeting PKM2 and LDHA Involving Glycolysis
Authors: Zhang Dan , He Zhiwei , Shen Yiyi , wang Jie , Liu Tao , Jiang Jianxin 
Published: August 2020

Abstract
Background: Malignant proliferation and chemotherapy resistance are some of the causes of high mortality in pancreatic cancer. MicroRNAs have long been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. miR-489-3p is involved in inhibiting the growth of many tumors, but its relationship with the growth and metabolism of pancreatic cancer is not clear. Methods：We used RNA in situ hybridization to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues. The qRT-PCR experiment detected the content of miR-489-3p in pancreatic cancer cell lines and ordinary pancreatic ductal epithelial cells. Then we did experiments in vivo (subcutaneous tumor formation in nude mice) and in vitro (plate cloning, transwell, glycolysis related experiments) experiments to verify that miR-489-3p can continue the invasion and metastasis of pancreatic cancer and glucose metabolism. Furthermore, we confirmed that LDHA and PKM2 are the two targets of miR-489-3p through dual luciferase reporter gene experiments. Finally, several reply experiments were done to verify the regulation mechanism of miR-489-3p.Results: We determined that miR-489-3p is under-expressed in pancreatic cancer tissues by RNA in situ hybridization, and the function acquisition and deletion experiments and glycolysis experiments confirmed that miR-489-3p can inhibit the proliferation and invasion of Glycolysis. We then analyzed the website to find that miR-489-3p can target LDHA and PKM, and then we verified this finding with a luciferase report experiment. Therefore, we proceeded with recovery experiments on LDHA and PKM2, and concluded that miR-489-3p performs its function by targeting LDHA and PKM2. Finally, in vivo experiments confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer. Conclusion: In short, we identified miR-489-3p as a novel chemotherapy target for pancreatic cancer, and its diagnostic value deserves further study.
Down-Regulated microRNA-421 Was Associated with the Poor Prognosis of Breast Cancer Patients
Authors: Zhang Keqian , Mao Tianqi , He Zhicheng , Wu Xiaojiao , Peng Yu , Chen Yanrong , Dong Yan , Ruan Zhihua , Wang Zhe 
Published: August 2020

Abstract
Background: Breast cancer is one of the most common cancers among females with high morbidity and mortality. MicroRNAs (miRNAs) have been reported to play important roles in the development of cancers. However, the prognostic value of microRNA-421 (miR-421) in breast cancer have not been extensively explored.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the relative expression of miR-421 in breast cancer tissue samples. Relationships between miR-421 expression and clinicopathological factors were analyzed by chi-square test. The effects of several variables on survival status were tested by Kaplan-Meier curve and Cox proportional hazards regression analyses.Results: MiR-421 expression was significantly decreased in breast cancer tissues, compared with adjacent noncancerous tissues (P<0.001). Moreover, abnormal miR-421 expression was closely correlated with lymph node metastasis (P<0.001), TNM stage (P=0.021), and differentiation (P=0.044) of breast cancer patients. Kaplan-Meier analysis revealed that patients with low miR-421 expression had a shorter overall survival time than those with high miR-421 expression (P=0.001). Furthermore, multivariate analysis demonstrated that miR-421 (P=0.014, HR=2.000, 95%CI: 1.149-3.480) was an independent prognostic indicator in breast cancer patients, as well as lymph node metastasis (P=0.016, HR=1.987, 95%CI: 1.137-3.474).Conclusion: The reduced expression of miR-421 may predict the poor prognosis of breast cancer and miR-421 may be involved in the progression of breast cancer.
miR-124&nbsp;Functions&nbsp;as A&nbsp;Marker&nbsp;in Diagnosing&nbsp;Colorectal Cancer
Authors: Yan Yang , Du Xiaohui , Xia Shaoyou , Li Songyan , Teng Da , Hu Shidong , Wang Yufeng , Li Rong 
Published: August 2020

Abstract
Background: MicroRNA-124 (miR-124) regulates cell growth, angiogenesis, invasion, and apoptosis of many human tumors. Our objective was to evaluate the levels of miR-124 in serum samples of colorectal cancer (CRC) patients to explore whether miR-124 in serum can be used as a biomarker for the detection of CRC.Methods: Serum miR-124 level was measured in 85 patients with CRC and 60 healthy control subjects using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). The correlations between miR-124 levels and clinicopathologic factors were analyzed. Diagnostic performance of serum miR-124 level was calculated by using the receiver operating characteristic (ROC) curve.Results: The expression level of miR-124 in serum samples was significantly lower in CRC patients than in healthy controls (P<0.001). A positive correlation between miR-124 level and tumor size (P=0.010), invasion depth (P=0.021), lymph node metastasis (P=0.015), and TNM stage (P=0.004) was observed. The serum miR-124 yielded an AUC (areas under the ROC curve) of 0.832 with a sensitivity of 80.0% and a specificity of 81.7%, and the optimal cutoff point of miR-124 was 1.61.Conclusions: Serum miR-124 may have a potential as a novel biomarker for the detection of CRC.
Identification of Hub Gene TIMP1 and Relative ceRNAs Regulatory Network in Colorectal Cancer
Authors: Kong De-jun , Qin Ya-fei , Li Guang-ming , Wang Hong-da , Zhao Yi-ming , Hao Jing-peng , Wang Hao 
Published: August 2020

Abstract
Objectives This study aimed to discover the ceRNAs network in pathophysiological development of human colorectal cancer (CRC) and to screen biomarkers for target therapy and prognosis by using integrated bioinformatics analysis.Methods Data on gene expressions of mRNAs, circRNAs, and miRNAs and clinical information were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database respectively. Differentially expressed mRNAs (DEGs) were identified by using DESeq2 package of R software. Functional enrichment analysis was conducted by ClusterProfiler package of R software. Protein-protein interaction (PPI) network was shown by STRING website. Survival analysis of hub genes was performed by survival package in R software. Interactions among hub gene, DEmiRNAs and DEcircRNAs were used to construct ceRNAs network.Results A total of 412 DEGs (including 82 upregulated and 330 downregulated) were screened out between 473 CRC and 41 normal samples. 260 DEcircRNAs (including 253 upregulated and 7 downregulated) were altered. A ceRNAs and PPI network was successfully constructed and TIMP1 associated with prognosis were employed.Conclusion The present study identifies a novel ceRNAs network, which imply that TIMP1 is a potential biomarker underlying the development of CRC, providing new insights for survival prediction and therapeutic target.
Exploring Mandarin Chinese Teacher's&nbsp;Knowledge Base in China and the US: A Comparative Case Study
Authors: Lew Moi Mooi , Liu Liu 
Published: August 2020

Abstract
This study aimed to explore Mandarin Chinese teachers’ knowledge base in two different sociocultural contexts by comparing graduate level’s Teaching Chinese As a Foreign Language (TCFL) teacher education program curricula in China and the United States. The unit of analysis included four TCFL teacher education programs in both countries. The program curricula were analyzed based on three domains of knowledge, i.e., subject matter knowledge, procedural knowledge, and contextual knowledge. The comparative study results revealed that both countries focus on different domains of knowledge. China emphasis subject matters knowledge and the US focuses more on procedural knowledge. This study suggested that the TCFL teacher education program curricula in China should modify to focus more on the processes of Chinese second language teaching. The findings also asserted that the US’s TCFL teacher education curricula should focus more on the Chinese language subject matter knowledge so that graduates possess in-depth content knowledge to handle students’ misconceptions in second language acquisition. Mandarin Chinese teachers in both countries possess different domains of knowledge.
Structural, magnetic and dielectric properties of ultrafine nickel substituted cobalt ferrite− reduced graphene oxide nanocomposites
Authors: Ambikeswari N. , Manivannan S. 
Published: August 2020

Abstract
Nickel substituted cobalt ferrite − reduced graphene oxide (NCF-RGO) composite was synthesized using a facile one-pot chemical co-precipitation method. The addition of graphene oxide (GO) leads to the dimensional decrease of NCF nanoparticles (< 10 nm) in the composite, which controls the magnetic and dielectric properties. Nickel with lower ionic radius, compared to cobalt and its substitution in the composite along with the incorporation of GO results in the transition of ferromagnetic to superparamagnetic ordering. A large magnetisation of 51.63 emu/g and a high dielectric constant of 3.92 x 10 6 (at 100 Hz) were also developed from the composite. The conjugated mechanism of magnetic combined electrical property, with a high charge–storing capability and tuneable magnetization, enables its potential use in magnetic flipping or switching devices and data storing systems.