bluuebunny/crossref_metadata_2025 huggingface dataset:
Nothing wrong about change: The adequate choice of the dependent variable and design in prediction of cognitive training success
Authors: Mattes André , Roheger Mandy
Published: August 2020

Background Even though investigating predictors of intervention success (e.g Cognitive Training, CT) is gaining more and more interest in the light of an individualized medicine, results on specific predictors of intervention success in the overall field are mixed and inconsistent due to different and sometimes inappropriate statistical methods used. Therefore, the present paper gives a guidance on the appropriate use of multiple regression analyses to identify predictors of CT and similar non-pharmacological interventions.Methods We simulated data based on a predefined true model and ran a series of different analyses to evaluate their performance in retrieving the true model coefficients. The true model consisted of a 2 (between: experimental vs. control group) x 2 (within: pre- vs. post-treatment) design with two continuous predictors, one of which predicted the success in the intervention group and the other did not. In analyzing the data, we considered four commonly used dependent variables (post-test score, absolute change score, relative change score, residual score), five regression models, eight sample sizes, and four levels of reliability.Results Our results indicated that a regression model including the investigated predictor, Group (experimental vs. control), pre-test score, and the interaction between the investigated predictor and the Group as predictors, and the absolute change score as the dependent variable seemed most convenient for the given experimental design. Although the pre-test score should be included as a predictor in the regression model for reasons of statistical power, its coefficient should not be interpreted because even if there is no true relationship, a negative and statistically significant regression coefficient commonly emerges.Conclusion Employing simulation methods, theoretical reasoning, and mathematical derivations, we were able to derive recommendations regarding the analysis of data in one of the most prevalent experimental designs in research on CT and external predictors of CT success. These insights can contribute to the application of considered data analyses in future studies and facilitate cumulative knowledge gain.
Structural Insights Into the Design of Peptide-based Drug or Diagnostic Reagent Antagonizing SARS-COV-2
Authors: jiang junhao , Deng Ping
Published: August 2020

Background

Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2.
Methods

Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted.
Results

Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development.
Conclusion

Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.
Increased Frequency of β Cells with Abnormal NKX6.1 Expression in Type 2 Diabetes but not in Subjects with Higher Risk for Type 2 Diabetes
Authors: Liu Tengli , Sun Peng , Zou Jiaqi , Wang Le , Wang Guanqiao , Liu Na , Liu Yaojuan , Ding Xuejie , Zhang Boya , Liang Rui , Wang Shusen , Shen Zhongyang
Published: August 2020

Background: NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation.Methods: Here, we obtained pancreata sections from organ donors, and aim to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM), and NKX6.1 and insulin immunofluorescence staining was performed.Results: Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1 Nuc- Ins + ), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1 cyt Ins - ) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation may mainly occur after T2DM was diagnosed.Conclusion: In sum, our results suggested that NKX6.1 expression in β cells is changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1 Nuc- Ins + and NKX6.1 cyt Ins - cells. This abnormality does not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM.
Experiences and Health-seeking Behaviour of Couples in Ekiti-State Nigeria towards Infertility
Authors: Esan Deborah Tolulope , Nnamani Kelechi Queedaline , Ogunkorode Agatha , Muhammad Fatimah , Oluwagbemi Olamide Oluyemisi
Published: August 2020

Background: Infertility has been described as the most important reproductive health concerns of Nigerian women. Based on the importance placed on offspring in the African context, infertility contributes to high level of psychological distress, conflicts between couples and subject those faced with the challenge to hazardous sexual behaviors. This study therefore explored the experiences and health-seeking behaviors of couples towards infertility.Methods: The study employed a qualitative research design. In-depth interviews were conducted with fifteen participants who had been diagnosed with primary or secondary infertility, who were currently receiving treatment at a tertiary health institution in the Ekiti State. Thematic categorization and content analysis was used to analyze the data. Results: Majority of the participant were Female (14 out of 15), between the ages of 20-35(80%) and are Christian (100%). All the participants reported negative emotional and psychological effects of infertility as they all expressed their unhappiness on the issue of infertility and claimed that the issue has affected them in all spheres of life (socially, marital relationship and psychologically). Two of the participants claimed that their husbands had abandon them because of their inability to conceive. Majority of the participants also claimed that there is social stigma associated with the condition as almost all (14 of 15) said the society is not doing anything to support women facing infertility issue. All the participants utilized medical treatments in combination with religious activities as a form of treatment. Conclusion: The society is not doing enough to support couples with infertility issue. Supports group should be created in the society where couples with similar challenge can come together to freely discuss and share their experiences as this could help in alleviating the psychological distress associated with infertility.
Isolation and Characterization of the Mycorrhiza Helper Bacteria from the Fairy Rings of Floccularia Luteovirens
Authors: xu minghang , Xing Rui , Gao Qing-bo , Zhang Fa-qi , Chen Shi-long
Published: August 2020

Floccularia luteovirens is an edible ectomycorrhizal fungus which forms fairy rings (FRs) distributed on the Qinghai-Tibet Plateau. Our previous study found four isolates of potential mycorrhiza helper bacteria (MHB), but they were only isolated from a single FR and their mycorrhizal promoting ability was not tested. Thus, it was necessary to collect samples from a larger area and measure the mycorrhizal promoting ability of the potential candidates. Of 184 bacterial isolates from five fairy rings located in Qinghai-Tibet Plateau belonging to 12 species, and 7 of them (58.3%) significantly promoting the growth of F. luteovirens. We also tested the symbiosis-promoting ability of the isolates, and the results showed that only four of them stimulated the formation of mycorrhizal symbiosis. This is the first report of the construction of mycorrhizal symbiosis between F. luteovirens and its host plant in greenhouse conditions. Our results showed that the strain A89 (Achromobacter marplatensis) could produce antifungal properties but nonetheless stimulated the fungal growth. This may due to the nutrient condition of medium and the genotype specificity of MHBs. The results suggest that the promotion of significant growth is not a good predictor for mycorrhiza formation promotion ability of MHB.
Metabolomic differences and interactions between coronary heart disease and diabetes mellitus: Pathogenesis understanding and auxiliary diagnosis
Authors: Liu Wuping , Guo Pengfei , Dai Tao , Shi Xiulin , Shen Guiping , Feng Jianghua
Published: August 2020

Background: Comprehensive understanding of plasma metabotype of diabetes (DB), coronary heart disease (CHD) and especially diabetes with coronary heart disease (CHDDB) has kept lacking. The metabolic fingerprints of CHD, DB and CHDDB were investigated to reveal their pathogenic mechanisms and interactions and identify their specific biomarkers.Methods: The plasma metabolomic differences and links of 15 DB, 15 CHD and 30 CHDDB patients and 15 matched healthy controls were investigated by NMR-based strategy. The univariate and multivariate statistical analyses-based pattern recognition was combined with network analysis to determine disease specific biomarkers and understand the corresponding pathogenic pathways.Results: A total of 17 metabolites related to the development of disease were identified by comparative metabolomic analysis, and 6 of them were shared by the three diseases. The metabolites involved in amino acid synthesis (valine, alanine, leucine, isoleucine, and N-acetyl-glycoprotein) were positively associated with CHD and CHDDB (Odds Ratios (OR) >1); The trimethylamine oxide, glycerol, lactose, indoleacetate and scyllo-inositol are closely related to the development of DB to CHDDB (OR>1), and indoleactate (OR: 1.06, 95% confidence interval (CI): 1.01-1.12) and lactose (OR: 2.46, 95% CI: 1.67-3.25) are particularly prominent in CHDDB. The three different multi-biomarker signatures could serve to distinguish between CHDDB, DB, and CHD. All diseases demonstrated the disturbed glycolysis/gluconeogenesis and amino acid biosynthesis pathway. Furthermore, inositol phosphate metabolism, tryptophan metabolism and microbiota metabolism play a major role in the development of CHDDB from DB.Conclusions: The disease-specific multi-biomarkers provide promising capability in auxiliary diagnosis of DB-related disease and follow-up of disease progression and treatment. The comparative metabolomics strategy of multi-diseases offers a comprehensive perspective in disease-specific markers and pathogenic pathways.
Loss of ATRX sensitizes HeLa cells in response to ionizing irradiation in a manner dependent on the ATM/Chk2 pathway
Authors: Tang Geng , Yang Yanming , Liu Yuxin , Han Bing , Xu Weiqiang , Qin Lijing , Fang Fang , Wang Zhicheng
Published: August 2020

Identifying novel targets for molecular radiosensitization is critical to improve the efficacy of cancer radiotherapy. Alpha-thalassemia/mental retardation X-linked (ATRX), a member of the SWI/SNF-like chromatin remodeling protein family, functions in the maintenance of genomic integrity, alternative lengthening of telomeres, and the regulation of apoptosis and senescence. However, whether ATRX is directly involved in the DNA damage response (DDR) remains unknown. Here, we show that silencing ATRX increased the sensitivity of cells to ionizing radiation (IR). IR-induced DNA damage was greater and G2/M arrest was less efficient in ATRX knockdown cells. ATRX downregulation caused defects in apoptosis and senescence, indicating that ATRX has a biological function in the DDR. ATRX loss led to failure to trigger ataxia telangiectasia-mutated (ATM) auto-phosphorylation, inhibiting the activation of ATM/Chk2 downstream effectors. These data identify ATRX as a novel target for radiosensitization, and its effect depends on inhibition of the ATM/Chk2 pathway in the DDR.
Promoting healthy foods in the new digital era: An experimental study on the effect of a popular versus fictitious ‘Insta-influencer’ on brand attitude and purchase intentions
Authors: Folkvord Frans , Roes Elze , Bevelander Kris
Published: August 2020

Background: Most studies on influencer marketing techniques have focused on the promotion of unhealthy foods whereas little is known about the promotion of healthier foods. The present experimental study investigated whether a popular real versus fictitious social influencer is more successful in promoting healthy food products. In addition, we examined the role of parasocial interaction as an underlying mechanism of healthy food product endorsement. Methods: We used a randomized between-subject design with 154 participants (age: 24.0 years). Viewers’ product attitude and purchase intention were tested after exposure to an Instagram post by a popular social influencer (n = 77) or fictitious social influencer (n= 77).Results: Results showed that parasocial interaction mediated the relation between the type of social influencer and product attitude as well as purchase intention. Parasocial interaction was higher for participants exposed to the popular influencer compared to the fictitious influencer, leading to higher healthy food brand attitude and purchase intentions. Discussion: The findings showed that it is crucial for influencers to establish a warm personal relationship and connection with the their followers when promoting a healthy product successfully. We suggest that the promotion of healthy foods could be more successful in public health when using popular social influencers.
Dapagliflozin activates AMPK to attenuate cardiac dysfunction and oxidative stress under hypoxia/reoxygenation-caused damage
Authors: Tsai Kun-Ling , Hsieh Pei-Ling , Chou Wan-Ching , Cheng Hui-Ching , Huang Yu-Ting , Chan Shih-Hung
Published: August 2020

Background: Emerging evidence demonstrated Dapagliflozin (DAPA), an inhibitor of type II sodium-glucose cotransporter-2, prevented various cardiovascular events. However, the detailed mechanisms underlying its cardioprotective properties remained largely unknown. In the present study, we sought to investigate the effects of DAPA on the cardiac ischemia/reperfusion (I/R) injury and study the mechanisms of DAPA-provided cardioprotection.Methods: For in intro studies, cardiac myoblast H9c2 cells were exposed to hypoxia with no-glucose medium for 1 hr than followed a reoxygenation with high-glucose medium for 4 hr. DAPA was treated before hypoxia/reoxygenation (H/R) exposure. For in vivo investigations, I/R was instigated in Sprague-Dawley (SD) rats using ligation of the left anterior descending coronary artery (LAD). DAPA was given daily by gavage for 5 days before I/R induction.Results: Results from in vitro experiments showed that DAPA induced the phosphorylation of adenosine 5'-monophosphate activated protein kinase (AMPK), resulting in the downregulation of phosphorylated protein kinase C (PKC) in the cardiac myoblast H9c2 cells following H/R condition. We demonstrated that DAPA treatment diminished the H/R-elicited oxidative stress via the AMPK/ PKC/ NADPH oxidase (Nox) pathway. In addition, DAPA prevented the H/R-induced abnormality of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) expression, mitochondrial membrane potential, and mitochondrial DNA copy number through AMPK/ PKC/ Nox signaling. Besides, DAPA reversed the apoptosis-associated changes, including H/R-suppressed Bcl-2 and H/R-induced expression of phosphorylated p53, Bax cytochrome c, and activated caspase 3 via AMPK/ PKC/ Nox/ PGC-1α signaling. Furthermore, we demonstrated that DAPA improved the I/R-induced cardiac dysfunction by echocardiography and abrogated the I/R-elicited apoptotic cells by terminal deoxynucleotidyl transferase dUTP nick end labeling assay in the myocardium of rats. Also, the administration of DAPA mitigated the production of two myocardial infarction markers, creatine phosphokinase isoenzymes and lactate dehydrogenase.Conclusion: In conclusion, our data suggested that DAPA treatment holds the potential to ameliorate the I/R-elicited oxidative stress and the following cardiac apoptosis via AMPK/ PKC/ Nox/ PGC-1α signaling, which attenuates the cardiac dysfunction caused by I/R injury.
Genome-Wide Identification and Functional Prediction of Circular RNAs in Response to Heat Stress in Chinese Holstein Cows
Authors: Qi Ying , Li Qiuling , Guo Yuemei , Chu Mingxing , Zhang Yiming , Guo Junfei
Published: August 2020

Background: Heat stress (HS) leads to substantial economic loss of dairy industry each year. The negative effect of HS in dairy cows is becoming one of the more urgent and important issue due to accelerating side-effects of global warming. At present, the best way to alleviate the effect of HS is breeding of thermotolerant cows which depends on the profound understanding of mechanism of HS. Various genes are involved in HS response but the information about the role of noncoding RNAs, especially circular RNAs (circRNAs) is largely unknown.Results: In our study, we aimed to investigate the different expression profile of circRNAs between HS and normal condition (NC) of Chinese Holstein cow’s mammary gland. CircRNAs were identified using RNA sequencing and bioinformatics analysis. In total, 37405 circRNAs were detected and 95 were differentially expressed (DE), including 15 downregulated and 80 upregulated circRNAs in HS group compared to NC. Eight circRNAs were randomly selected to verify the RNA sequencing result. Further, Sanger sequencing validated the backsplicing site of the eight circRNAs. Moreover, results obtained from the Quantitative real time PCR (qRT-PCR) showed consistent expression trend with that of RNA sequencing. GO annotation and KEGG analysis suggested that these DE circRNAs probably involved in the energy metabolic regulation. Furthermore, we constructed ceRNA network and the result indicated that these DE circRNAs could regulate lactation through IGF1 and PRL signaling pathway.Conclusion: During our study, it was evident that circRNAs were involved in regulation of HS response in Chinese Holstein cow’s mammary gland. This will help researchers to achieve a better understanding of mechanism related to HS response and can provide new insights in breeding of thermotolerant dairy cows.
Flexor Hallucis Longus Hypertrophy Secondary to Achilles Tendon Tendinopathy: An MRI-based Case-Control Study
Authors: Wirth Stephan , Andronic Octavian , Aregger Fabian , Jungwirth-Weinberger Anna , Jentzsch Thorsten , Hecker Andreas
Published: August 2020

Background: The purpose of this study was to outline indirect signs of advanced Achilles tendinopathy on magnetic resonance imaging (MRI) and develop a potential tool that could aid in surgical decision-making.Methods: Magnetic resonance imaging (MRI) scans of Achilles tendon were analyzed retrospectively in two consecutive cohorts. Control group consisted of patients that had an MRI due to other reasons and no signs of tendinopathy. Two parameters from two muscle bellies were measured and compared on axial MRI scans 4 to 5 cm above the ankle joint line at the level of greatest thickness: area and diameter of the triceps surae (TS) and of the flexor hallucis longus (FHL). Interobserver agreement was analyzed. A receiver operating characteristic (ROC) curve was created for both quotients to assess potential cut-off points.Results: A total of 60 patients for each study group were included. The ratios for area and for diameter showed significant higher values for FHL in the tendinopathy group (p<0.001). There was strong to very strong interobserver agreement (rho=0.744). A diameter ratio FHL/TS of 2.0 or higher had a sensitivity of 49% and specificity of 90% for concomitant Achilles tendinopathy.Conclusion: In our patient cohort, flexor hallucis longus hypertrophy was observed even before a tendon transfer was employed as a possible compensatory mechanism for Achilles tendon tendinopathy. Using the tool described in this study, measuring a value of 2.0 or higher on an axial MRI, may be indicative as an indirect sign of functional deterioration of the Achilles tendon.
Differential Expression of Members of SOX Family of Transcription Factors in Failing Human Hearts
Authors: Liu Chia-Feng , Ng Ying , Thachil Varun , Morley Michael , Moravec Christine S , Tang W. H. Wilson
Published: August 2020

Background: The Sry-related high-mobility-group box (SOX) gene family, with 20 known transcription factors in humans, plays essential roles during development and in many disease processes. Several SOX proteins, e.g., SOX4, SOX11, and SOX9, are required for normal heart morphogenesis. SOX9 was shown to contribute to cardiac fibrosis in animal models. However, differential expression of other SOX transcription factors and their functional roles in the failing human myocardium have not been explored.Methods and Findings: All 20 SOX genes from RNA-seq data were extracted, and their RNA levels were compared to the NF, DCM, and hypertrophic cardiomyopathy (HCM) groups. The protein levels of the differential expressed SOX genes were confirmed by Western blot. Four SOX genes whose RNA levels were significantly upregulated in DCM or HCM compared to NF. However, only SOX4 and SOX8 proteins were markedly increased in the heart failure groups. Gene co-expression network analysis identified genes associated and respond similarly to perturbations with SOX4 in cardiac tissues. Using a meta-analysis combining epigenetics and genome-wide association data, we reported several genomic variants associated with HF phenotype linked to SOX4 or SOX8.Conclusions: Elevation of SOX8 and SOX4 are observed in the failing human myocardium. The molecular mechanism associated with them in HF warrants further investigation.
Prognostic Significance of Lymph Node Metastases and Ratio in Laryngeal Squamous Cell Carcinoma
Authors: Wang Zhihai , Li Yanshi , Lu Tao , Liu Chuan , Hu Guohua
Published: August 2020

Background

The lymph node metastases (LNM) and the lymph node ratio (LNR) were shown to be prognostic factors in head and neck cancer. The purpose of this study was to investigate the prognostic significance of the LNM and LNR in patients with laryngeal squamous cell carcinoma (LSCC).
Methods

All patients undergoing resection of laryngeal cancer at the First Affiliated Hospital of Chongqing Medical University between March 2011 and December 2018 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves estimated using the Kaplan-Meier method.
Results

Of 670 patients with LSCC, the median overall survival (OS) of was 42.2 months, and 3-year and 5-year OS rates were respectively 92.9 ± 1.1% and 86.1 ± 1.7%. 12.69% (85/670) were pathological nodal positive (pN+). LNM was associated with tumor site, T stage and differentiation degree (p < 0.05). And the 5-year OS rates in the pathological nodal negative (pN-) and pN + groups were 88.7± 1.7% and 69.9 ± 5.9%, respectively (p = 0.000), and the presence of pN + was the most significant prognostic factor for survival. Furthermore, the 5-year OS of patients with 1 to 3 positive LN and 4 or more positive LN were 64.6±8.1% and 44.9 ± 15.2%, respectively (p = 0.032). Additionally, LNR examination did not reach significance in our study. However, it demonstrates that increasing LNR was associated with worsening survival.
Conclusion

LNM is an independent prognostic factor in LSCC, and increasing number of positive LN and LNR in patients portend a poor prognosis.
Development of the General Self-regulation Scale for a Healthy Lifestyle (GSRSHL) among Japanese University Students
Authors: Wang Yiran , Urban Robert , Rigó Adrien , Kato Yoshiko
Published: August 2020

Background: A healthy lifestyle of students is an important contributor to both quality of life and longevity. The objective of this study was to develop a new measurement scale, the General Self-regulation Scale for a Healthy Lifestyle (GSRSHL), for university students. Methods: A total of 434 university students (281 male, 153 female) participated in this study. To confirm the validity of the new scale, we examined the relationship among the GSRSHL, the Japanese version of the Brief Self-control Scale, perceived stress, and life satisfaction.Results: The exploratory factor analysis of 15 items yielded two correlated factors: “planning achievement” and “emotional control.” The new scale showed good internal consistency. Confirmatory factor analysis with covariate analysis demonstrated that “planning achievement” and “emotional control” were positively associated with self-regulation and life satisfaction. “Emotional control” related negatively to perceived stress. “Planning achievement” increased the odds of adequate sleep, balanced diet, and physical exercise. “Emotional control” increased the odds of consuming breakfast, having adequate sleep, following a balanced diet, and having less stress.Conclusions: Our study provided evidence of the validity and the applicability of the GSRSHL in Japanese students.
Identification of potential prognostic markers for osteosarcoma by integrated analysis
Authors: Ge Yuxiang , Ding Wang , Bian Chong , Gu Huijie , Xu Jun , Yin Xiaofan
Published: August 2020

Background: Osteosarcoma (OS) is the most common type of musculoskeletal malignant tumor, accounting for over 30% of primary skeletal sarcomas. Although great efforts have been made, the mechanism of OS still remains largely unknown. In this study, we aim to identify gene modules and representative candidate biomarkers for clinical diagnosis of patients with OS, and reveal the mechanisms of OS progression.Methods: Weighted gene co-expression network analysis (WGCNA) was conducted to construct a co-expression network and investigate the relationship between modules and clinical traits. Functional enrichment analysis was performed on module genes. Protein-protein interaction (PPI) network was constructed to identify the hub gene and the expression level of hub genes was validated based on another dataset.Results: A total of 9854 genes were included in WGCNA, and 17 gene modules were constructed. Gene module related with OS in sacrum was mainly enriched in skeletal system development, bone development and extracellular structure organization. Furthermore, we screened the top 10 hub genes and further validated 5 of the 10 (MMP13, DCN, GNG2, PCOLCE and RUNX2), the expression of which were upregulated as compared with normal tissues.Conclusion: The hub gene we identified show great promise as prognostic markers for the management of OS and our findings also provide new insight for molecular mechanism of OS.
tRFTar: Identifying The Targets of tRNA-Derived Fragments
Authors: Xiao Qiong , Gao Peng , Huang Xuanzhang , Chen Xiaowan , Chen Quan , Lv Xinger , Fu Yu , Song Yongxi , Wang Zhenning
Published: August 2020

Background: The tRNA-derived fragments (tRFs) are 14–40 nucleotides, small non-coding RNAs from specific tRNA cleavages, and they have key regulatory functions in many biological processes. Many studies showed that tRFs are associated with Argonaute complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools to accurately predict tRF target genes. Methods: We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous Argonaute-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including sequence context of each individual site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF predicting models. Results: We first identified features that globally influenced tRF targeting. Among them, the most significant ones were minimum free folding energy (MFE), position 8 match, number of bases paired in tRF-mRNA duplex, and length of tRF, which were consistent with previous findings. We built the model with the area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977-0.983) in the training process and AUC = 0.847 (0.83-0.861) in the test process. The model was applied to all the sites with perfect Watson-Crick complementarity to the seed in the 3'-UTR of human genome. Seven of nine target / non-target genes of tRFs confirmed by reporter assay were predicted. Conclusions: Predictions can be obtained online, tRFTar, freely available at http://trftar.cmuzhenninglab.org:3838/tar/, which is the first tool to predict targets of tRFs in human with a user-friendly interface.
Identification of Key Genes with Clinical Outcome in Benign Meningioma Using Bioinformatic Analysis
Authors: Cao Ming , Shen Chen , Zhu Jie , Wang YuHai
Published: August 2020

Background: Meningioma is the second most common type of brain neoplasms.However,the underlying molecular mechanisms are still not clear,and the main treatment is mainly surgery plus radiotherapy. Material and method: To explore the key genes in benign meningioma,we downloaded microarray dataset GSE43290 from Gene Expression Omnibus(GEO) database.The differential genes (DEGs) between benign meningioma and normal meninges were identified by GEO2R.The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway were performed by the Database for Annotation,Visualization and Integrated Discovery (DAVID).The protein-protein interaction (PPI) network and module analysis were performed and visualized by the Search Tool for the Retrieval of Interacting Gene database (STRING) and Cytoscape.The hub genes were evaluated by the Cytohubba and further explored by MCODE plugin of Cytoscape and Enrichr.The relationship between hub genes and clinical factors were further explored by GSE16581 through R software. Result: A total of 358 DEGs were identified,including 15 upregulated genes and 343 downregulated genes.The main enriched functions were extracellular matrix organization、inflammatory response、cell adhesion、extracellular space and integrin binding.The main KEGG pathways were Malaria and focal adhesion.Among these DEGs,5 overlapping genes(CXCL8、AGT、CXCL2、CXCL12、CXCR4) were selected as hub genes.CXCL2 and CXCL8 were correlated with age and tumor recurrence,which could be clinical therapeutic targets. Conclusion: This study indicates the key genes in benign meningioma which may help us understand the molecular mechanisms and provide the candidate therapeutic targets.
Propofol Stimulates Immune Activity and Decreases Inflammatory Cytokines via NF-κB-Mediated JAK1-STAT3 Pathway in Gastric Cancer Patients Undergoing Radical Surgery
Authors: Zhang Haili , Qian Shi , Jing Wang
Published: August 2020

BackgroundPropofol is the most commonly used general anesthesia for patients with gastric cancer undergoing radical surgery. Studies have suggested that propofol exerts beneficial effects on the immune function of patients with cancer. However, the potential mechanism underlying propofol-mediated immune regulation remains to be elucidated. The present study investigated the regulatory effects of propofol on immune function in patients with gastric cancer undergoing radical surgery. MethodsELISA, reverse transcription-quantitative polymerase chain reaction, western blotting, gene transfection and immunohistochemistry were used to analyze the effects of propofol on gastric cancer cells.ResultsResults demonstrated that propofol general anesthesia resulted in an increased percentage of cluster of differentiation (CD)4+ and CD8+ cells, increased serum concentrations of interleukin (IL)-2 and tumor necrosis factor (TNF)-α, decreased serum concentrations of IL-1β and IL-8 following propofol general anesthesia in gastric cancer patients undergoing radical surgery compared with midazolam. In addition, propofol general anesthesia induced an imbalance in T helper (Th)1/Th2 cells, increased the number of natural killer cells and B cells, decreased the expression of prognostic factors, and improved tumor metastasis, recurrence and survival in patients with gastric cancer compared with midazolam. Furthermore, immunohistochemistry demonstrated that propofol downregulated nuclear factor (NF)-κBp65, and upregulated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) expression level in gastric cancer tissues, downregulated the protein expression levels of NF-κBp65, JAK1, STAT3, TNF-α, IL-1β and IL-8 protein expression in gastric cancer cells isolated from gastric cancer tissues. NF-κBp65 overexpression inhibited propofol-mediated upregulation of JAK1, STAT3, TNF-α, IL-1β and IL-8 expression in gastric cancer cells. ConclusionsThese data indicate that that propofol may increase the number of T cells, stimulate T-cell proliferation, upregulate IL-2 and TNF-α expression, and enhance immune function via the NF-κB-mediated JAK1-STAT3 signaling pathway in patients with gastric cancer undergoing radical surgery.
Small dense low-density lipoprotein cholesterol is an effective target marker for predicting cardiovascular events and laser treatment for retinopathy in diabetic patients
Authors: Nakayama Atsuko , Morita Hiroyuki , Sato Tatsuyuki , Kawahara Takuya , Takeda Norifumi , Kato Satoshi , Itou Hiroshi , Komuro Issei
Published: August 2020

Background

Small dense low-density lipoprotein cholesterol (sdLDL-C) has been recently reported as a sensitive marker for cardiovascular diseases.
Objective

We explored the superiority of sdLDL-C as a marker for predicting cardiovascular (CV) events and the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.
Methods

We performed a sub-analysis of the intEnsive statin therapy for hyper-cholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study (n = 5042), in which patients were assigned randomly to intensive or standard statin therapy targeting low-density lipoprotein cholesterol < 70 mg/dl or 100–120 mg/dl. Using the Cox hazard analysis and Kaplan-Meier analysis, the risks for CV events and the need for laser treatment were evaluated according to the following lipids: total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B (ApoB), and sdLDL-C one year after registration.
Results

The patients were 63 ± 11 years old and 48% of them were male. LDL-C and sdLDL-C levels were 98 ± 25 and 32 ± 14 mg/dl, respectively, one year after registration. The sdLDL-C level had a strong positive correlation with ApoB level (r = 0.83). SdLDL-C was a sensitive marker for predicting CV events when comparing among the quartiles according to sdLDL-C levels (hazard ratios: HR for quartiles 1–4 were 1.0, 1.4, 1.6, and 2.5, respectively; p for trend < 0.01). Also, sdLDL-C was a sensitive marker for predicting the need for laser treatment among lipids (log rank, p = 0.009), especially in patients with elderly (> 65 yrs) and obesity (BMI > 25 kg/m2).
Conclusions

SdLDL-C is a sensitive target marker to predict cardiovascular events as well as the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.
Trial registration:
UMIN000003486, www.umin.ac.jp/ctr/.
Association of AGT rs2493132 Polymorphism and the Risk of Coronary Artery Disease in Patients with Non-alcoholic Fatty Liver Disease in Chinese Han Population
Authors: Dong Mengzhen , Zhang Jie , Ma Xuefeng , Wang Mengke , Wang Yifen , Liu Shousheng , Yongning Xin
Published: August 2020

Background: Previous studies proved that AGT gene polymorphisms were associated with the serum lipids metabolism; however, it is not clear whether AGT rs2493132 increases the risk of NAFLD and CAD. This study was designed to investigate the relationship between AGT rs2493132 gene polymorphism and the developing risk of NAFLD and CAD in Chinese Han population.Methods: A total of 142 NAFLD patients, 109 NAFLD + CAD patients, and 246 health controls were included in this study. PCR method was used to measure AGT genotype. The anthropometric and clinical data were measured in clinical laboratory department of Qingdao Municipal Hospital. Statistical analyzes were conducted using the SPSS statistical software, version 21.0. Results: The AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD (OR = 1.785; 95%CI: 1.061-3.003; P = 0.029), and the risk of CAD in patients with NAFLD was still marked after adjusted for gender, age, and BMI (OR = 4.718; 95%CI: 1.502-14.824; P = 0.008). The T allele of AGT rs2493132 also significantly increased the risk of CAD in NAFLD patients (OR = 2.436; 95% CI: 1.184-5.011, P = 0.016) after adjusted for age, gender, and BMI. In addition, AGT rs2493132 T allele carriers possess the higher TC and LDL levels compared to the non-carriers in all the participants (Both P < 0.05).Conclusions: AGT rs2493132 CT + TT genotype and T allele significantly increased the developing risk of CAD in the patients with NAFLD in Chinese Han population. AGT rs2493132 T allele associated with the increased serum TC and LDL levels.
Changes in psychological distress and quality of life after esophageal cancer surgery: A prospective study
Authors: Kim Jeong Hye , Jung Ju Ri
Published: August 2020

Background

Esophageal cancer patients experience physical and psychological difficulties after surgery. This study aimed to identify the changes in psychological distress and quality of life in patients with esophageal cancer before surgery to three months after surgery.
Methods

We enrolled 49 patients who were scheduled to undergo esophageal surgery at a tertiary hospital in Seoul, South Korea in this prospective study. Patients’ psychological distress and quality of life were assessed with the Korean scales HADS, EORTC QLQ-C30, and QLQ-OES18 at the pre-surgery, one-month post-surgery, and three months post-surgery.
Results

Moderate-to-severe depression was reported in 12.2% of patients at the pre-surgery evaluation, in 57.1% of patients one-month post-surgery, and 8.2% of patients three-months post-surgery. Moderate-to-severe depression was reported in 12.2% of patients at the pre-surgery evaluation, in 63.3% of patients one-month post-surgery, and 16.3% of patients three months post-surgery. Clinically significant, moderate changes (10–20 points) in physical functioning, insomnia, nausea and vomiting, and dyspnea, and significant, large changes (> 20) in role functioning, fatigue, pain, and appetite loss (per EORTC QLQ-C30) were reported from pre-surgery to one-month post-surgery. Clinically significant, moderate changes (10–20 points) in dysphagia and taste problems and a significant, large change (> 20) in eating difficulties (per QLQ-OES18) were reported from pre-surgery to one-month post-surgery.
Conclusion

One month after esophageal cancer surgery, patients demonstrated severe psychological distress and worsening quality of life.
Integrated transcriptome and proteome analysis provides insights into leaf color differences between red-leaved poplar cultivars (‘Quanhong’ and ‘Xuanhong’) and ‘Zhonglin 2025’ (Populus deltoides cv. ‘Zhonglin 2025’)
Authors: Chen Xinghao , Liu Hanqi , Wang Shijie , Zhang Chao , Yang Minsheng , Zhang Jun
Published: August 2020

BackgroundThe red-leaved poplar cultivars ‘Quanhong’ and ‘Xuanhong’ are bud mutations of Populus deltoides cv. ‘Zhonglin 2025’. These cultivars are valued for their beautiful shape, lack of flying catkins, and ornamental leaf colors. The molecular mechanism that leads to different leaf colors between these red-leaved poplars and ‘Zhonglin 2025’ remains unclear.ResultsIn this study, we analyzed growth and physiological indicators in the ‘Quanhong’, ‘Xuanhong’, and ‘Zhonglin 2025’ poplar cultivars, and performed transcriptome and proteome analysis of their leaves. The results showed that plant height and ground diameter were significantly lower in both red-leaved poplars than in ‘Zhonglin 2025’, indicating that their growth and development were markedly inhibited. The ratio of anthocyanin to total chlorophyll and photosynthetic capacity of the leaves were higher and lower, respectively, in the red-leaved cultivars than in ‘Zhonglin 2025’. At the transcript and protein levels, 6,792 differentially expressed genes (DEGs) and 2,786 differentially expressed proteins (DEPs) were screened in the ‘Quanhong’ cultivar, respectively, and 4,398 DEGs and 2,333 DEPs were screened in the ‘Xuanhong’ cultivar, respectively. We screened 769 DEGs/DEPs in ‘Quanhong’ and 399 DEGs/DEPs in ‘Xuanhong’ in an integrated transcriptomics/proteomics analysis. Based on the results of this integrated analysis, 15 and 11 genes/proteins involved in anthocyanin synthesis were further identified in ‘Quanhong’ and ‘Xuanhong’, respectively, including the CHS , F3H , and DFR genes. Among the 120 transcription factors, 3 (HY5, HYH, and TTG2), may be directly involved in the regulation of anthocyanin synthesis in both red-leaved poplars.ConclusionsBy comparing the proteomes and transcriptomes of red-leaved poplar cultivars and ‘Zhonglin 2025’, we identified the key genes and proteins related to red leaf coloration. The findings of this study provided insights that may aid further studies of the molecular mechanism of leaf red coloration in red-leaved poplars.
Correlation between perioperative parecoxib and postoperative acute kidney injury in patients undergoing non-cardiac surgery: a retrospective cohort analysis
Authors: Tang Yongzhong , Zeng Pingping , Liao Yan , Qin Zheng , Zhang Hao , Li Bo , Ouyang Wen , Li Dan
Published: August 2020

Background: The association of nonsteroidal anti-inflammatory drugs with postoperative acute kidney injury is controversial. However, there are few studies focusing on the association between parecoxib and postoperative acute kidney injury. Methods: We retrospectively reviewed the electronic medical records and laboratory results of 9,246 adult patients (18–60 years) undergoing non-cardiac surgery at Third Xiangya Hospital of Central South University from January 1, 2012 to August 31, 2017. Study groups were either treated with or without parecoxib. Univariable analysis identified demographic, preoperative laboratory, and intraoperative factors associated with acute kidney injury. Logistic stepwise regression was used to calculate the adjusted odds ratio of parecoxib and acute kidney injury association. Results: The incidence of postoperative acute kidney injury was 6.06% and parecoxib was used in 0.105% of patients. The mortality was 4.64% in the acute kidney injury group. The incidence of acute kidney injury was lower in the parecoxib-administered group (4%) than in the without parecoxib-administered group (6.3%, p = 0.005). Postoperative acute kidney injury risk reduced by 33.40% in the parecoxib-administered group after adjusting for interference factors.Conclusions: Intraoperative single-dose parecoxib (40 mg or 80 mg) might reduce postoperative acute kidney injury risk in adult patients undergoing non-cardiac surgery.
Tet2 inactivation enhances the anti-tumor activity of tumor-infiltrating lymphocytes (TILs) to curtail melanoma growth
Authors: Lee Minjung , Li Jianfang , Fang Shaohai , Zhang Joanna , Vo Anh , Han Wei , Zeng Hongxiang , Isgandarova Sevinj , Martinez-Moczygemba Margarita , Han Weidong , Zhou Yubin , Li Jia , Sun Deqiang , Huang Yun
Published: August 2020

Inactivation of tumor infiltrating lymphocytes (TILs) is one of the mechanisms mitigating anti-tumor immunity during tumor onset and progression. Epigenetic abnormalities are regarded as a major culprit contributing to the dysfunction of TILs within tumor microenvironments. In this study, we used a murine model of melanoma to discover that Tet2 inactivation significantly enhances the anti-tumor activity of TILs, with the efficacy comparable to immune checkpoint inhibition imposed by anti-PD-L1 treatment. Single-cell RNA-seq analysis further revealed that Tet2-deficient TILs exhibit effector-like features. Transcriptomic and ATAC-seq analysis further demonstrated that Tet2 deletion reshapes the chromatin accessibility and favors the binding of transcription factors geared toward CD8+ T cell activation. In summary, our study establishes that Tet2 constitutes one of the epigenetic barriers contributing to dysfunction of TILs, and that Tet2 inactivation could benefit anti-tumor immunity to boost tumor suppression.
A plasma membrane protein based prognostic model in clear cell renal cell carcinoma
Authors: Liu Haosheng , Fang Jianxiong , Liu Tianqi , Zhang Zhenhui , Zhao Chao , Peng Tianming , Li Yong , Pu Xiaoyong , Liu Jiumin
Published: August 2020

Background

Renal cell cacinoma (RCC) accounts for 3% of human cancers, and clear cell renal cell carcinoma (ccRCC) is the most common pathological type of RCC. Cell surface proteins have been shown to play an important role in the occurrence and progression of various cancers. In this study, we focused on plasma membrane proteins (PMPs), to explore their potential value in ccRCC.
Methods

The PMPs expression profiles and ccRCC patients’ clinical information were downloaded from TCGA database. Through a series of bioinformatic methods, we established a plasma membrane proteins prognostic model.
Results

Multivariate cox regression analysis and area under receiver operating characteristic curve indicated that this model was an effective independent predictor of ccRCC clinical outcomes. Combined with other two clinical characteristics, a nomogram was constructed to predict patient survival at 1, 3, and 5 years.
Conclusions

Our study is the first to explore the prognostic value of plasma membrane proteins in clear cell renal cell carcinoma. We hope our work could provide a new viewpoint for ccRCC prognosis and drawn people’s attention to plasma membrane proteins in clear cell renal cell carcinoma.