bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Pharmacology and Component Analysis Integrated Study to Unveil Molecular Mechanisms of A Traditional Chinese Medicine Decoction (Polygonum Multiflorum, Rehmannia Glutinosa, Senna Obtusifolia and Crataegus) in Hypertension Treatment
Authors: Lem Fui Fui , Opook Fernandes , Lawson Fahcina P. , Yong Thau Lym Wilson , Chee Fong Tyng 
Published: June 2020

Abstract
Background: Traditional Chinese Medicines (TCM) are known for their curative effects on hypertension through a holistic approach. The molecular mechanisms of the formulation comprising Polygonum multiflorum, Rehmannia glutinosa, Senna obtusifolia and Crataegus, used by Chinese practitioners in ameliorating hypertension, however remain a mystery. This initial study is thus aimed at unveiling the molecular mechanisms of this TCM formulation in treating hypertension. Methods: The methanolic extract compounds of the decoction were identified through Liquid chromatography mass spectrometry-mass spectrometry (LC-MS/MS). Oral bioavailability and drug likeness were then measured to filter out identified compounds. Several databases, such as the SwissTargetPrediction, STRING, OMIM and KEGG, were used to retrieve information on the predicted targets for the purpose of developing a network using Cytoscape Version 3.8. Enrichment analysis was then performed to elucidate the mechanisms of the decoction in hypertension mitigation. Results: A total of 11 compounds identified were revealed to possess bioavailable and drug like characteristics, based on the Veber and Quantitative Estimation of Drug-likeness (QED) parameters. Pathway analysis showed enrichment of pathways such as cardiac muscle contraction, fluid shear stress and atherosclerosis, dilated cardiomyopathy, renin-angiotensin system and hypertrophic cardiomyopathy (HCM), which are all strongly associated with hypertension. Conclusion: The network pharmacology analysis clearly shows that this TCM decoction ameliorates hypertension through several indirect pathways where most of the targets are involved in HCM, which is caused by hypertension.
Inhibition of Fibroblast Activation by Components of Rhizoma Curcumae and Rhizoma Sparganii in A Rat Model of Uterine Leiomyoma
Authors: Feng Yewen , Zhao Yumin , Li Yao , Peng Teng , Kuang Yu , Shi Xingming , Wang Gang , Peng Fu , Yu Chenghao 
Published: June 2020

Abstract
Background: Traditional Chinese medicine (TCM) often uses Rhizoma Curcumae and Rhizoma Sparganii (RCRS) ，the natural herbs for the treatment of UL. RCRS has been shown to be effective in the treatment of UL in our previous study. This study was to investigate the molecular mechanism by which RCRS inhibits fibroblast activation protein (FAP) activation and prevents uterine leiomyoma in rats. Methods: The SD rat model of uterine leiomyoma was established by estrogen and progesterone load combined with external stimulation. Subsequently, histological analyses, enzyme-Linked immunosorbent assays, western blotting were performed to evaluate the effect of the drug on uterine leiomyoma and its mechanism. Results: Our data showed that treatment of rats with RCRS significantly reduced the expression of FAP, TGF-β (the FAP activating factor), and significantly decreased the phosphorylation of cell proliferation pathway-related signaling factors AKT/MEK/ERK, as well as the expression of the extracellular matrix component collagen. Conclusions: Our results showed that RCRS is very effective in prevention and treatment of uterine leiomyoma in rats, and RCRS may exert its actions by inhibiting the activation of tumor-associated fibroblasts, inhibiting the cell proliferation, and improving tumor extracellular matrix.
A Framework for Addressing Multiple Ecosystem Services in Forest Management Planning
Authors: BASKENT Emin Zeki , BORGES Jose Guilherme , KASPAR Jan 
Published: June 2020

Abstract
Background: Forest policy and decision makers are challenged by the need to balance the increasing demand for multiple ecosystem services while addressing the impacts of natural disturbances (e.g. wildfires, droughts, wind, insect attacks) and global change scenarios (e.g. climate change) on its potential supply. This challenge provides the motivation for the development of a framework for incorporating concerns with a wide range of ecosystem services in multiple criteria management planning contexts. Thus, the paper focused on both the analysis of the current state-of-the art in forest management planning and the development of a conceptual framework to accommodate various components in a forest ecosystem management planning process.Results: Based on a thorough recent classification of forest management planning problems and the state-of-the-art research, the key dimensions of that framework and the process were defined. The emphasis is on helping identify how concerns with a wide range of ecosystem services may be analyzed and better understood by forest ecosystem management planning. This research discusses the potential of contemporary management planning approaches to address multiple forest ecosystem services. It highlights the need of a landscape-level perspective and of spatial resolution to integrate multiple ecosystem services. It discusses the importance of methods and tools that may help support the involvement of stakeholders and public participation in hierarchical planning processes. Conclusions: The research addressed the need of methods and tools that may encapsulate the ecological, economic and social complexity of forest ecosystem management to provide an efficient plan, information about tradeoffs between ecosystem services as well as the sensitivity of the plan to uncertain parameters (e.g. prices, climate change) in a timely manner.
Identification of AREG, STAG3, C19orf57 and CAV1 as key prognostic factors in HPV- negative head and neck squamous cell carcinoma
Authors: Tian Guocai , Fu You , Li Jiang , Zhang Zhiyuan , Yang Xi 
Published: June 2020

Abstract
Background Head and neck squamous cell carcinoma (HNSCC) is a common tumor worldwide with poor prognosis. The pathogenesis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs differs. However, few studies have considered the HPV status when identifying biomarkers for HNSCC. Thus, the identification of biomarkers for HPV-positive and HPV-negative HNSCCs is urgently needed. Methods Three microarray datasets from Gene Expression Omnibus (GEO) were analyzed, and the differentially expressed genes (DEGs) were obtained. Then, functional enrichment pathway analysis was performed and protein-protein interaction (PPI) networks were constructed. The expression of hub genes at both the mRNA and protein level was determined in Oncomine, The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). In addition, survival analyses of the patient stratified by HPV status and the expression levels of key genes were performed based on TCGA data. The role of AREG, STAG3, CAV1 and C19orf57 in cancer were analyzed through Gene set enrichment analysis (GSEA). Finally, the top ten small molecule drugs were identified and the therapeutic value of zonisamide, NVP-AUY922, PP-2 and fostamatinib was further evaluated in six HPV-negative HNSCC cell lines. Results In total, 47 DEGs were obtained, 11 of which were identified as hub genes. Biological process analysis indicated that the hub genes were associated with the G1/S transition of the mitotic cell cycle. Survival analysis uncovered that the prognostic value of AREG, STAG3, C19orf57 and CAV1 differed between HPV-positive and HPV-negative patients. Gene set enrichment analysis (GSEA) showed the role of AREG, STAG3 and CAV1 in dysregulated pathways of tumor. Ten small molecules were identified as potential drugs specifically for HPV-positive or HPV-negative patients; three—NVP-AUY922, fostamatinib and PP-2—greatly inhibited the proliferation of six HPV-negative HNSCC cell lines in vitro. Conclusions In conclusion, AREG, STAG3, C19orf57 and CAV1 are key prognostic factors and potential therapeutic targets in HPV-negative HNSCC. NVP-AUY922, fostamatinib and PP-2 may be effective drugs for HPV-negative HNSCC.
RAPD and ERIC-PCR coupled with HRM for species identification of non-dysenteriae Shigella species isolated from clinical specimens; As a potential of alternative method
Authors: Pakbin Babak , Basti Afshin Akhondzadeh , Khanjari Ali , Azimi Leila , Karimi Abdollah 
Published: June 2020

Abstract
Background: Shigella species cause gastrointestinal disorders and diarrhea in adults and children, also known as fatal and invasive pathogens for infants and neonates. Species identification of Shigella isolates are so prominent for epidemiological studies and implementing infection prevention strategies. At the present study, we developed and evaluated RAPD and ERIC-PCR assays coupled with HRM for differentiation of non-dysenteriae Shigella species as potential alternative methods. isolation of eighteen Shigella strains from faecal specimens collected from children under 2 years old with diarrhea symptom (n=143), species of the isolates were identified by slide agglutination assay as the golden standard method. Species of isolates were identified using developed RAPD-PCR-HRM and ERIC-PCR-HRM assays and differentiation of data sets obtained from difference plots of HRM was implemented by PCA as a dimension reduction method then sensitivity and specificity of the methods were evaluated using ROC curve. Results: Consequently, we found that RAPD-PCR-HRM with sensitivity and specificity of 100 and 85% respectively is significantly more suitable for identification of non-dysenteriae Shigella species. However, sensitivity and specificity of ERIC-PCR-HRM were evaluated 33 and 46% respectively.Conclusion: Regardless of inherent poor reproducibility of DNA fingerprinting based methods, RAPD-PCR-HRM assay can be considered as a potential of alternative method for species identification. Also, HRM technique used in this study is more rapid, inexpensive, and sensitive than gel electrophoresis for characterization of PCR amplicons.
Antimicrobial Activity Testing Methods for Hydrophobic Patterned Surfaces
Authors: Perez-Gavilan Ana , Castro Joana Vieira de , Arana Ainara , Merino Santos , Retolaza Aritz , Alves Sofia A , Francone Achille , Kehagias Nikolaos , Sotomayor-Torres Clivia M. , Cocina Donato , Mortera Renato , Crapanzano Salvatore , Pelegrín Carlos , Garrigos María del Carmen , Jiménez Alfonso , Galindo Begoña , Araque Mari Carmen , Dykeman Donna , Neves Nuno M. , Marimón Jose María 
Published: June 2020

Abstract
Background: One strategy to decrease the incidence of hospital-acquired infections is to avoid the survival of pathogens in the environment by the development of surfaces with antimicrobial activity. To study the antimicrobial behaviour of active surfaces, different approaches have been developed of which ISO 22916 is the standard. Aim: To assess the performance of different testing methodologies to analyse the antimicrobial activity of hydrophobic surface patterned plastics as part of a Horizon 2020 European research project (FLEXPOL: Antimicrobial FLEXible POLymers for its use in hospital environments No. 721062).Methods: Four different testing methods were used to study the antimicrobial activity of a patterned film, including the ISO 22916 standard, the immersion method, the touch-transfer inoculation method, and the swab inoculation method, this latter developed specifically for this project.Findings: The non-realistic test conditions of the ISO 22916 standard showed this method to be non-appropriate in the study of hydrophobic antimicrobial patterned surfaces. The immersion method also showed no differences between patterned films and smooth controls due to the lack of attachment of testing bacteria on both surfaces. The antimicrobial activity of films could be demonstrated by the touch-transfer and the swab inoculation methods that more precisely mimicked the way of high-touch surfaces contamination. Conclusion: The touch-transfer and the swab inoculation methods proved to be the best methodologies to test the antimicrobial activity of patterned hydrophobic surfaces. In our opinion, a new ISO standard should be developed on the basis of these tests to study the antimicrobial behaviour of patterned surfaces.
Cloning, Purification, and Characterization of a Novel Metagenome-Sourced Microbial Chitinase with Dual Catalytic Domains
Authors: Dai Yumei , Yang Feng , Liu Xiao , Wang Hongling , Yan Zhiying 
Published: June 2020

Abstract
Background: Microbial chitinases have attracted a lot of attention because of their great potential in many applications. Metagenome-based approach obtains the target genes from the environment directly without culturing the microbes and is becoming a powerful tool to discover the novel chitinases. Results: A metagenomic approach was used to discover the chitinases from a wetland on the Qinghai-Tibetan plateau. Gene P1724 was found and predicted to have two GH18 catalytic domains. Gene sequence containing P1724 , only its N-terminal GH18 domain ( P1724nGH18 ) or only C-terminal GH18 domain ( P1724cGH18 ) were cloned and expressed in Escherichia coli BL21 (DE3). These purified recombinant chitinases showed maximum hydrolytic activities at 40 °C, pH 5.0-6.0 and 0-0.5 M NaCl, and were cold adaptive since they were still active at 4 °C. The activities of three chitinases were decreased with the presence of Cu 2+ and EDTA, but increased with Ba 2+ and Ca 3+ . All three chitinases showed both chitotiosidase and endochitinase activities, and produced predominantly N, N΄-Diacetylchitobiose from colloid chitin. Other than these common characteristics, P1724 and P1724nGH18 shared more similarity in temperature and pH stabilities, NaCl tolerance and substrate affinity, suggesting the N-terminal GH18 domain contributed more than the C-terminal GH18 did in biochemical characteristics of P1724. k cat / K m value (catalytic efficiency) of P1724 was significantly higher than the sum values of P1724nGH18 and P1724cGH18’s, which indicated that two GH18 domains of P1724 works synergistically in degrading chitin. Conclusion: Compared to the most of microbial chitinases containing only one catalytic domain, chitinases P1724 with two GH18 catalytic domains was discovered firstly by the metagenomic approach. P1724 is a novel chitinase with unique amino acid sequences and hydrolytic mode, and could be used in cold environments or industries.
Cardamonin Enhances Cisplatin Chemosensitivity of Nasopharyngeal Cancer Cells via Attenuating c-Myc-Mediated β-Catenin/ABCG2 Signaling
Authors: Qiao Liang , Li Rongzhen , Wu Yahui , Wang Yujie , Wang Bin , Wang Guangke 
Published: June 2020

Abstract
Purpose: Resistance to chemotherapeutic drugs in nasopharyngeal carcinoma(NPC) remains a major obstacle of clinical therapy. To address the issue, screening for natural low-toxicity products as chemosensitizers has become a promising strategy for cancer therapy. In this study, we investigated chemosensitizing effects of cardamonin (CM), a plant-derived chalcone, on cisplatin (DPP)-resistant NPC cells, and explored the molecular mechanism for its antitumor activity. Methods: The chemotherapeutic efficacy of cardamonin, cisplatin and their combination in cisplatin-resistant NPC cells were analyzed using MTT assay, apoptosis assay, and cell cycle analysis. Real-time PCR, western blotting, and cell transfection analysis were performed to assess the synergistic inhibitory action of cardamonin supplemented with cisplatin on Wnt/β-catenin/ABCG2 signaling. The effect of cardamonin on ABCG2 drug efflux function was analyzed by doxorubicin accumulation assay. A CNE2/DPP nude mouse model was used to determine the combinatorial effects of cardamonin on tumor growth in vivo. Results: Cardamonin increased cisplatin-induced cytotoxicity, accompanied by induction of apoptosis and cell cycle arrest in DPP-resistant NPC cells. Moreover, cardamonin could synergized with cisplatin to downregulate β-catenin, c-Myc, and ABCG2. Specifically, cardamonin inhibited Wnt/β-catenin/ABCG2 signaling through c-Myc-mediated transcription inactivation, thereby suppressing the expression of ABCG2 in cisplatin-resistant NPC cells. These findings were confirmed in vivo, wherein cardamonin treatment with cisplatin resulted in reduced tumor growth in a CNE2/DPP xenograft animal model. Conclusions: Taken together, our data firstly demonstrated that cardamonin increased chemosensitivity of nasopharyngeal cancer cells to cisplatin through inactivation of Wnt/β-catenin/ABCG2 signaling, more specifically by inhibition of β-catenin/ABCG2 signaling through c-Myc-mediated transcriptional inactivation, thereby downregulation of ABCG2 and reversal of cisplatin resistance. Thus, in addition to its chemotherapeutic potential, cardamonin may serve as a useful chemosensitizer to conventional chemotherapeutic drugs in the treatment of nasopharyngeal carcinoma.
Prognostic Implications of Pan-cancer CMTM6 Expression and Its Relationship With the Immune Microenvironment
Authors: Zhang Minghui , Zhao Yanbin , Pu Haihong , Guo Shengyue , Zhang Shuai , Wang Yan 
Published: June 2020

Abstract
Background: CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) reportedly stabilizes programmed death-ligand 1 (PD-L1) and enhances the efficacy of immunotherapy. However, correlations between CMTM6 expression and the immune microenvironment and its prognostic value remain unknown in a variety of tumors.Methods: CMTM6 expression data were obtained from The Cancer Genome Atlas (TCGA) for 33 cancer types classified into high and low expression subgroups according to the median CMTM6 expression value. Pan-cancer analysis of CMTM6 protein expression in 20 tumor types was performed using a cohort from the Human Protein Atlas (HPA). PD-L1 protein expression data were obtained from The Cancer Proteome Atlas (TCPA) for 32 cancer types. Frequencies of CMTM6 copy number alterations and mutations were analyzed using cBioPortal. MANTIS was employed to estimate microsatellite instability in the TCGA cohort. CIBERSORT and the ESTIMATE algorithm were applied to estimate the relative fractions of infiltrating immune cell types and immune scores, respectively. Kaplan–Meier survival curve analysis was performed to assess the pan-cancer prognostic value of CMTM6.Results: CMTM6 is heterogeneously expressed in diverse cancers. Further, the results revealed low CMTM6 mutation frequencies in multiple cancers. Among them, CMTM6 mutation frequency was the highest in uterine cancer. Additionally, CMTM6 expression was related to PD-L1 protein expression in breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, sarcoma (SARC), stomach adenocarcinoma, and uterine carcinosarcoma. Increased CMTM6 expression may be associated with increased infiltration of neutrophils in some types of cancer. Finally, pan-cancer analysis indicated that CMTM6 expression was closely related to overall survival in adrenocortical carcinoma, GBM, acute myeloid leukemia, liver hepatocellular carcinoma, mesothelioma, SARC, thymoma, and uveal melanoma. Conclusions: Taken together, these findings highlight that CMTM6 plays an important role in the tumor immune microenvironment, and CMTM6 has been identified to have prognostic value in some types of cancers.Thus, CMTM6 is a potential target for cancer immunotherapy and an effective prognostic biomarker.
Identification of an Immune-related Seven-lncRNA Signature Predicting Prognosis and Tumor-infiltrating Immune Cells in Lung Adenocarcinoma
Authors: Wu Jinchun , Mou Yanhua , Zhang Chunfang , Duan Chaojun , Li Bin 
Published: June 2020

Abstract
Background: Lung adenocarcinoma (LUAD) is a common cancer. Immunotherapy is one of the major treatments but showing diverse efficacy in LUAD. Long non-coding RNAs (lncRNAs) are emerging as important players in immune regulation in cancer. Herein, we identified and validated a prognostic signature of immune-related lncRNAs in LUAD and explored its correlation with tumor-infiltrating immune cells (TIICs) by bioinformatics analysis.Methods: Immune-related lncRNAs were acquired using Pearson correlation analysis between lncRNAs from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and immune genes from the ImmPort website and Molecular Signatures Database. The risk signature was constructed in the TCGA group through univariable Cox, lasso and multivariable Cox regression analyses. The prognostic value of the established risk signature was validated in both TCGA and GEO datasets. The interacted TIICs and immune pathways with each single lncRNA and the risk signature were investigated respectively in ImmLnc database, Cibersortx database and gene set enrichment analysis (GSEA) analyses.Results: A seven immune-related lncRNAs prognostic signature was constructed and it stratified LUAD into high and low risk groups. High risk group showed poorer overall survival (OS) in comparison with low risk group via survival analysis.The seven-lncRNAs signature was closely correlated with various TIICs and immune pathways mostly involved in T cell activation, antigen processing and presentation, chemokines and cytokine receptors.Conclusions: The seven lncRNAs model was identified as a predictable signature for prognosis of LUAD patients probably due to its immunomodulation role. This study might provide a new target for enhancing the efficacy of immunotherapy in this mortal disease.
A study of the international stock market crash and recovery during COVID-19 pandemic using a modified chaos game representation
Authors: Gupta Aman , Shaju Cyril , Pratibha  , Kamal  
Published: June 2020

Abstract
This paper deals with a novel approach to visualize and compare financial markets across the globe using chaos game representation of iterated function systems. We modified a widely used fractal method to study genome sequences and applied it to study the effect of COVID-19 on global financial markets. We investigate the financial market reaction and volatility to the current pandemic by comparing its behavior before and after the onset of COVID-19. Our method clearly demonstrates the imminent bearish and a surprise bullish pattern of the financial markets across the world.