bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplex Immunohistochemistry Indicates Biomarkers in Colorectal Cancer
Authors: Zhang Wen , Song Zhengji , Zhang Baoyue , Wang Jinli , Guo Qiang , Sun Zhiwei , Tang Hui 
Published: November 2020

Abstract
Background : Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, whose survival ratio and indicating biomarkers are limited. The rapid development of multiple immunofluorescence gives rise to widespread applications of this newly advanced technology called multiplex immunohistochemistry (mIHC), which makes it possible to detect several fluorescent proteins on the same tumor tissue microarray (TMA) within the same time and spatial organization. Methods : By taking advantage of this mIHC technology, we detected three tumor-associated antigens (TAA) including the human epidermal growth factor receptor 2 (HER2), the cluster of differentiation 133 (CD133), the programmed death ligand-1 (PD-L1) and one immune-associated macrophage marker, the cluster of differentiation 68 (CD68) in cancer tissues versus para-carcinomatous normal tissues derived from a cohort of 84 CRC patients. Results: All the four markers were upregulated in cancer tissue compared with normal tissues. And the expressions of CD133, HER2, PD-L1 and CD68 were correlated with pathological grade, T stage, tumor size, metastasis, respectively. Accordingly, CD133 and PD-L1 could be applied as potential diagnostic biomarkers for CRC at early stage, while the enrichment of HER2 might act as an advanced indicator in aggressive cancer status of CRC; whereas, CD68 could be potentially considered as an advanced diagnostic indicator in CRC patients, as well as a metastatic promoter in CRC-related TME. Conclusions : The differential expression of these four proteins, as well as their clinicopathological correlation indicates that these four proteins could be utilized as diagnostic and prognostic biomarkers in CRC patients.
Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins and Candidate Drugs in Renal Papillary Cell Carcinoma
Authors: Jiang Silin , Ren Xiaohan , Liu Shouyong , Lu Zhongwen , Xu Aiming , Qin Chao , Wang Zengjun 
Published: November 2020

Abstract
Background: Roles of RNA binding proteins in renal papillary cell carcinoma (KIRP) remain undiscovered. We thus conducted a series of bioinformatics analyses to elucidate the associations between RBPs and prognosis of renal papillary cell carcinoma.Methods: RNA sequencing data and clinical of KIRP were downloaded from the TCGA database. The differentially expressed RBP coding genes (DEGs) were sorted out by R software and Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed to evaluate the functional pathways. Protein-protein interaction (PPI) network of DEGs was formed through the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape. Subsequently, a prognostic model was constructed by the uses of univariate Cox regression analysis, random survival forest analysis and multivariate Cox analysis. Validations of Receiver Operating Characteristic (ROC) analysis, KM analysis of overall survival and nomogram were performed as follow. Furthermore, CMap database was used to predict potential drugs.Results: A prognostic OS-predictive model based on six RBPs (SNRPN, RRS1, INTS8, RBPMS2, IGF2BP3 and PIH1D2) was constructed. STOCK1N-28457, pyrimethamine and trapidil were determined as potential drugs according to the CMap database.Conclusion: This study constructed a prognosis-related six-RBP signature and made a prediction of three small molecular drugs, which provided a novel insight into KIRP and assisted the development of individualized therapeutic strategies.
Human Drug Efflux Transporter ABCC5&nbsp;Confers Sensitivity and Acquired Resistance to Pemetrexed in Breast Cancer
Authors: Chen Jihui , Wang Zhipeng , Gao Shouhong , Wu Kejin , Bai Fang , Zhang Qiqiang , Wang Hongyu , Ye Qin , Xu Fengjing , Sun Hong , Lu Yunshu , Liu Yan 
Published: November 2020

Abstract
AimPemetrexed, a new generation antifolate drug, is approved for the treatment for locally advanced or metastatic breast cancer, but factors affecting the efficacy and resistance of it have yet to be fully explicit. ATP-binding cassette transporters have been reported as prognostic and adverse effects predictors of many xenobiotics. This study was designed to explore whether ABC transporters affect pemetrexed resistance and may contribute to treatment regimen optimization for breast cancer.MethodsFirstly, the expression of ABC transporters family members was measured in cell lines, thereafter examined the potential role of ABC transporter in conferring resistance to pemetrexed in primary cancer cell lines isolated from 34 breast cancer patients, and then the role of ABCC5 in mediating transport of pemetrexed and apoptosis pathway in MCF-7 cell lines was assessed. Finally, the functions of ABCC5 on therapeutic effect of pemetrexed was evaluated in breast cancer bearing mice.ResultsThe expressions of ABCC2, ABCC4, ABCC5 and ABCG2 were significantly increased in pan-resistance cell lines, and the ABCC5, the most obvious one, was 5.21 times higher than that of the control group. The expression of ABCC5 was inversely correlated with sensitivity (IC50) of pemetrexed (r = 0.741; p<0.010) in breast cancer cell lines from 34 patients. Further, we found expression of ABCC5 influenced the efflux and cytotoxicity of pemetrexed in MCF-7 cell line, and the IC50 were 0.06 μg/ml and 0.20 μg/ml in ABCC5 knock-down and over-expression cells, respectively. In vivo study, we found ABCC5 affected sensitivity of pemetrexed in breast cancer bearing mice, and the tumor volume was much larger in ABCC5 over-expression group than that in control group (2.7 folds vs 1.2 folds).ConclusionsOur results indicated ABCC5 was associated with pemetrexed sensitivity and resistance in vitro and in vivo, and may be a biomarker for regimen optimization of pemetrexed in breast cancer treatment.
Knowing Cancer Diagnosis is a Protective Factor for the Survival of Patients With Breast Cancer : A Retrospective Cohort Study
Authors: He Chen , Zhu Wenxi , Tang Yunxiang , Bai Yonghai , Luo Zheng , Xu Jinfang , Wang Hao , Xu Shuyu , Xu Jingzhou , Xiao Lei , Zhang Ruike , Wang Yajing , Du Jing , Huang Yujia , Li Xiaopan , Su Tong 
Published: November 2020

Abstract
Background: The health burden of breast cancer is rising in China. The effect of informed diagnosis on long-term survival has not been fully understood. This retrospective cohort study aims at exploring the association between early informed diagnosis and survival time in breast cancer patients.Methods: 12,327 breast cancer patients were enrolled between October 2002 and December 2016. Potential factors including knowing cancer diagnosis status, gender, age, clinical-stage, surgical history, the grade of reporting hospital and diagnostic year were registered. We followed up all participants every 6 months until June 2017.Results: By June 2017, 18.04% of the participants died of breast cancer. Both the 3-year and 5-year survival rate of whom knew cancer diagnosis were longer (P<0.001). By stratified analysis, except subgroups of male patients and patients in stage III, patients knowing diagnosis showed a better prognosis in all the other subgroups (P<0.05). By Cox regression analysis, it was showed that not knowing cancer diagnosis was an independent risk factor for survival in breast cancer patients (P<0.001).Conclusions: Being aware of their cancer diagnosis plays a protective role in extending the survival time in breast cancer patients, which suggests medical staff and patients’ families disclose cancer diagnosis to patients timely.
Study on Mechanism of γ-PGA&nbsp;and Nattokinase Produced by Bacillus Subtilis Natto Based on RNA-Seq Analysis
Authors: Li Min , Zhang Zilong , Li Shenwei , Tian Zhengan , Ma Xia 
Published: November 2020

Abstract
Poly-γ-glutamic acid (γ-PGA) and nattokinase (NK) are the main substances produced by Bacillus subtilis natto in solid-state fermentation and have wide application prospects. We found that our strains have higher nattokinase activity when soybean is used as a substrate to improve the yield of γ-PGA. Commercial production of γ-PGA and nattokinase requires an understanding of the co-production mechanism. Here, we monitored the metabolites of the fermentation process firstly, analyzed the transcriptome of Bacillus subtilis natto when co-producing γ-PGA and NK, and obtained the maximum γ-PGA yield (11.39 ± 0.38%, w/w) and highest activity of NK during fermentation. By comparing the up-regulated genes and down-regulated genes of key enzymes and product-related metabolic pathways for genetic engineering, the co-production mechanism of γ-PGA and nattokinase can be summarized. This study firstly provides new insights into the co-production mechanism of γ-PGA and nattokinase by Bacillus subtilis natto, and reveals potential molecular targets for promoting the co-production of γ-PGA and nattokinase.
Degradation of Penicillin G by Visible Light Irradiation-Assisted Biotransformation by Whole Cell paracoccus sp .
Authors: Wang Peng , Shen Chen , Cong Qinqin , Lu Jialin , Wang Xiaochun 
Published: November 2020

Abstract
Background: The Paracoccus sp. strain (KDSPL-02) isolated from sludge was identified and evaluated for catalytic activity in the degradation of penicillin G. Results: High degradation efficiency and synergistic catalytic effects of the whole cell and visible light without additional catalysts were observed. The key factors influencing the degradation and kinetics of penicillin G were investigated. The results showed the phenylacetic acid, which was produced during penicillin G biodegradation, exhibited stronger inhibiting effects on KDSPL-02. However, this effect was reduced by visible light irradiation without any additional photocatalyst; furthermore, the rate of penicillin G biodegradation was accelerated, reaching a 100% rate in 12 h at a penicillin G concentration of 1.2 g/L. Four key intermediates produced during penicillin G degradation were isolated and identified by LC–MS, 1H NMR, and 13C NMR. Enzymes involved in the PAA pathway were proposed from a genomic analysis of paracoccus sp. KDSPL-02. Conclusions:These results provide a new method for bio-degrading of penicillin or other antibiotic pollutants using photoaccelerating biocatalysts with greater efficiency and more environmentally friendly conditions.
Modulation of Gastrointestinal Bacterial in Chronic Atrophic Gastritis Model Rats by Chinese and West Medicine Intervention
Authors: Huang Minghan , Li Sihan , He Youcheng , Lin Cuili , Sun Yueming , Li Mingzhu , Zheng Rong , Xu Ruoying , Lin Ping , Ke Xiao 
Published: November 2020

Abstract
Chronic atrophic gastritis (CAG) was well-known related with multiple pathogenic factors and normally therapies comprised by western or Chinese medicines. Present study was design to identified the bacterial community characterized by 16S rRNA amplicon sequencing and determine the modulate affection of bacterial composition response western and Chinese medicine Qing huayin (QHY) as well as antibiotic on model rats. Result shown the overall structure alteration of bacterial appeared under medicine applied, antibiotic caused a marked depletion in bacterial diversity and richness, the enrichment of Firmicutes (85.1-90.7%) in antibiotic-free convert to Bacteroidetes (30.7-34.6%) in antibiotic-added model rat were demonstrated. Firmicutes was most dominant phylum and accounting for 85.1%-90.5% and significantly decreased till 21.9%-68.5% in antibiotic-added treatments. Especially QHY-treated show highest RA of Firmicutes (90.5%) and the amelioration of CAG using QHY attributed by beneficial bacterial enrichment, especially Ruminococcus, Lactobacillus and Bifidobacterium. In addition, alpha and beta diversity analysis also demonstrated the clear dispersion and aggregation that revealed the alteration and steady of bacterial community structures. In summary, QHY has potential application value in the treatment of CAG which attributed to close relation with the modulatory of internal bacterial communities.
Nitrogen Transfer Play an Important Role of Differentially Expressed Protein of Roots in Eucalyptus Urophylla × E. grandis and Dalbergia Odorifera Nursery Seedlings Intercropping System
Authors: Yao Xianyu , Liao Liangning , Huang Yongzhen , Fan Ge , Yang Mei , Ye Shaoming 
Published: November 2020

Abstract
Background: The mixing of Eucalyptus with N2-fixing trees is a frequently successful and sustainable cropping practice. In this study, we evaluated nitrogen transfer and conducted a proteomic analysis on seedlings of Eucalyptus and a N2-fixing tree, Dalbergia (D.) odorifera, from intercropping and monocropping systems, to elucidate the physiological effecting and the molecular mechanisms on N transfer of Eucalyptus mixed with D. odorifera. Results: We demonstrated the following: (1) Nitrogen transfer occurred from D. odorifera to E. urophylla × E. grandis by 14.6 %. Interspecific facilitation of N uptake and root growth in E. urophylla × E. grandis was increased in the intercropping system, but the root growth and N absorption of D. odorifera were inhibited. (2) Among differentially expressed proteins was greater than 1.5 times, E. urophylla × E. grandis were found to be up-regulated several proteins for the nitrogen assimilation and enhancing the nitrogen competition, such as the proteins related to tricarboxylic acid/organic transformation, nitrogen metabolism and nitrogen assimilation; it also up-regulated the expression of stress resistant protein for its adaptability. However, the assimilation and metabolism of nitrogen was promoted in D. odorifera through the up-regulation of amino acid metabolism related proteins, and increased the key enzyme abundance of glycolysis pathway in D. odorifera. (3) Importantly, E. urophylla × E. grandis was the beneficiary in the process of N transfer, there were more different proteins involved in the synthesis pathway than that of the metabolic pathway, but there were more functional proteins involved in metabolic degradation in D. odorifera. Additionaly, the two groups of nitrogen compound transporter were found in E. urophylla × E. grandis, i.e. the molecular mechanism of the N transfer from D. odorifera to E. urophylla × E. grandis was explained by proteomics. Conclusions: Our study suggests that N transfer occurred from D. odorifera to E. urophylla × E. grandis and it was affected by the variations in the differentially expressed protein. We anticipate the result can be verified in field experiments for the sustainable development of Eucalyptus plantations.
Enhanced Aluminum Tolerance in Sugarcane: Evaluation of SbMATE Overexpression and Genome-wide Identification of ALMTs in Saccharum Spp.
Authors: Ribeiro Ana Paula , Vinecky Felipe , DUARTE KAROLINE ESTEFANI , Santiago Thaís Ribeiro , Casari Rafael Augusto das Chagas Noqueli , Hell Aline Forgatti , Cunha Bárbara Andrade Dias Brito da , Martins Polyana Kelly , Centeno Danilo da Cruz , Cançado Geraldo Magela de Almeida , Magalhães Jurandir Vieira , Kobayashi Adilson Kenji , De Souza Wagner Rodrigo , Molinari Hugo Bruno Correa 
Published: November 2020

Abstract
BackgroundA major limiting factor for plant growth is the aluminum (Al) toxicity in acidic soils, especially in tropical regions. The exclusion of Al from the root apex through root exudation of organic acids such as malate and citrate are both the most ubiquitous tolerance mechanisms in the plant kingdom. Two families of anion channels that confer Al tolerance are well described in the literature, ALMT and MATE family. ResultsIn this study, sugarcane plants constitutively overexpressing the Sorghum bicolor MATE gene (SbMATE) showed improved tolerance to Al when compared to non-transgenic (NT) plants, characterized by sustained root growth and exclusion of aluminum from the root apex based on the result obtained with hematoxylin staining. In addition, genome-wide analysis of the recently released sugarcane genome identified 11 ALMT genes and molecular studies showed potential new targets for aluminum tolerance. ConclusionsOur results indicate that the transgenic plants overexpressing the Sorghum bicolor MATE has an improved tolerance to Al. The expression profile of ALMT genes revels potential candidate genes to be used has an alternative for agricultural expansion in Brazil and other areas with aluminum toxicity in poor and acid soils.
KLF7/VPS35 Axis Contributes to Hepatocellular Carcinoma Progression through CCDC85C-activated β Catenin Pathway
Authors: Guo Yarong , Chai Bao , Jia Junmei , Yang Mudan , Li Yanjun , Zhang Rui , Wang Shumin , Xu Jun 
Published: November 2020

Abstract
Objective: Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods: CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Human HCC tissues were collected to study the clinical significance VPS35 and β-catenin. Results: Firstly, KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Conclusion: We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.
Age-structured Impact of Mitigation Strategies on COVID-19 Severity and Deaths in Kenya
Authors: Mwalili Samuel , Kimathi Mark E. M. , Ojiambo Viona N. , Gathungu Duncan K. , Achia Thomas N. O. 
Published: November 2020

Abstract
Introduction: COVID-19, a coronavirus disease 2019, is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There have been a lot of attempts to model this pandemic from a global perspective. The Novel Coronavirus is still spreading quickly in several countries and the peak has not yet been reached in many countries. We developed age-structured model for describing the COVID-19 pandemic in Kenya under different non-pharmaceutical interventions. The first case in Kenya was identified in March 13, 2020 with the pandemic increasing to 465 confirmed cases by end of 3rd May, 2020. We fitted an age-structured deterministic mathematical model in Kenyan context.Methods: We model the COVID-19 situation in Kenya using Age-structured Susceptible Exposed Infectious Recovered compartmental model. These compartments follow a cascade of the disease from the Susceptible to Exposed individuals who in return are either symptomatic or asymptomatic. The symptomatic depict mild signs, which can develop to severe symptoms warranting hospitalization or can otherwise recover. The severe cases can recover with some developing critical condition. The critical are admitted at intensive care units. The resulting age-dependent ordinary differential equations from the model are solved using fourth order Runge-Kutta methods. We controlled for school closure, social distancing and lockdown in terms of movement restrictionsResults: The model shows varying epidemic peak by age-structure and the mitigation scenarios. The peak dates for unmitigated (UM), the 45% NPI (M45) and School closure-curfew-partial lockdown NPI (SCL) are May 21st, October 17th and December 13th 2020, respectively. Their respective cumulative infections peaks are 43M, 24M and 25M. The daily reported severe cases, critical cases and death proportionately increased with age. Conclusions: The cumulative number of infections reduces greatly with introduction of school closure, social distancing and restricted movement in highly affected counties. The degree of COVID-19 severity increases with age. However, it is not immediately clear when these restrictions can be lifted.
What is the Efficacy and Safety of Rapid Exercise Tests for Exertional Desaturation in Covid-19: A Rapid Systematic Review&nbsp;
Authors: Kalin Asli , Javid Babak , Knight Matthew , Inada-Kim Matt , Greenhalgh Trisha 
Published: November 2020

Abstract
BackgroundEven when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We sought to summarise the literature on the performance of different rapid tests for exertional desaturation. Main research questionWhat tests have been formally evaluated for the rapid assessment of exertional hypoxia in patients with lung disease against a gold standard exercise test such as the 6MWT and CPET? MethodAMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases were searched to September 2020. Studies where participants had Covid-19 or another lung disease and underwent any form of exercise test which was compared to a reference standard were eligible. Risk of bias was assessed using QUADAS 2. Heterogeneity of study design precluded meta-analysis. ResultsOf 47 relevant papers, 15 were empirical studies, of which 11 described an attempt to validate one or more exercise desaturation tests in lung diseases other than Covid-19. In all but one of these, methodological quality was poor or impossible to fully assess. None had been designed as a formal validation study (most used simple tests of correlation). Only one validation study (comparing a 1-minute sit-to-stand test [1MSTST] with the reference standard 6-minute walk test [6MWT] in 107 patients with interstitial lung disease) contained sufficient raw data for us to calculate the sensitivity (88%), specificity (81%), and positive and negative predictive value (79% and 89% respectively) of the 1MSTST. The other 4 empirical studies included two predictive studies on patients with Covid-19, and two on HIV-positive patients with suspected pneumocystis pneumonia. We found no studies on the 40-step walk test (a less demanding test that is widely used in clinical practice to assess Covid-19 patients). DiscussionExertional desaturation tests have not yet been validated in patients with (or suspected of having) Covid-19. Whilst there is limited evidence for the diagnostic accuracy of the 1MSTST in other diseases, specific features of this disease (e.g. exertional hypoxia is common and many assessments are done remotely with no clinician present to resuscitate) may raise safety issues. The less strenuous 40-step walk test should be urgently evaluated.