Consistency and Consensus Driven for Hesitant Fuzzy Linguistic Decision Making with Pairwise Comparisons

Hesitant fuzzy linguistic preference relation (HFLPR) is of interest because it provides an efficient way for opinion expression under uncertainty. For enhancing the theory of decision making with HFLPR, the paper introduces an algorithm for group decision making with HFLPRs based on the acceptable consistency and consensus measurements, which involves (1) defining a hesitant fuzzy linguistic geometric consistency index (HFLGCI) and proposing a procedure for consistency checking and inconsistency improving for HFLPR; (2) measuring the group consensus based on the similarity between the original individual HFLPRs and the overall perfect HFLPR, then establishing a procedure for consensus ensuring including the determination of decision-makers weights. The convergence and monotonicity of the proposed two procedures have been proved. Some experiments are furtherly performed to investigate the critical values of the defined HFLGCI, and comparative analyses are conducted to show the effectiveness of the proposed algorithm. A case concerning the performance evaluation of venture capital guiding funds is given to illustrate the availability of the proposed algorithm. As an application of our work, an online decision-making portal is finally provided for decision-makers to utilize the proposed algorithms to solve decision-making problems.Comment: Pulished by Expert Systems with Applications (ISSN: 0957-4174

Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2

Background: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism. Methodology/Principal Findings: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K-d values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2. Conclusion/Significance: In this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.National Basic Research Program of China [2010CB732402]; National Instrumentation Program [2011YQ03012412]; Natural Science Foundation of Fujian Province for Distinguished Young Scholars [2010 J06004]; National Found for Fostering Talents of Basic Science [J1030415

Consistency and consensus driven for hesitant fuzzy linguistic decision making with pairwise comparisons

Hesitant fuzzy linguistic preference relation (HFLPR) is of interest because it provides an efficient way for opinion expression under uncertainty. For enhancing the theory of group decision making (GDM) with HFLPR, the paper introduces a method for addressing the GDM based on consistency and consensus measurements, which involves (1) defining a hesitant fuzzy linguistic geometric consistency index (HFLGCI) and proposing an algorithm for consistency checking and inconsistency improving for HFLPR; (2) proposing a worst consensus index based on the minimum similarity measure between each individual HFLPR and the overall perfect HFLPR in order to build a consensus reaching algorithm based on the acceptable HLFPRs. The convergence and monotonicity of the proposed two procedures is proved. Experiments are performed to investigate the critical values of the defined HFLGCI, and comparative analyses are conducted to show the effectiveness of the proposed method. A case concerning the performance evaluation of venture capital guiding funds is given to illustrate the applicability of the proposed method. As an application of our work, an online decision-making portal is finally provided for decision makers to utilize the proposed method to solve GDM with HFLPRs

Reciprocal Regulation of Metabolic Reprogramming and Epigenetic Modifications in Cancer

Cancer cells reprogram their metabolism to meet their demands for survival and proliferation. The metabolic plasticity of tumor cells help them adjust to changes in the availability and utilization of nutrients in the microenvironment. Recent studies revealed that many metabolites and metabolic enzymes have non-metabolic functions contributing to tumorigenesis. One major function is regulating epigenetic modifications to facilitate appropriate responses to environmental cues. Accumulating evidence showed that epigenetic modifications could in turn alter metabolism in tumors. Although a comprehensive understanding of the reciprocal connection between metabolic and epigenetic rewiring in cancer is lacking, some conceptual advances have been made. Understanding the link between metabolism and epigenetic modifications in cancer cells will shed lights on the development of more effective cancer therapies

Glc7/PP1 dephosphorylates histone H3T11 to regulate autophagy and telomere silencing in response to nutrient availability

How cells adapt their gene expression to nutritional changes remains poorly understood. Histone H3T11 is phosphorylated by pyruvate kinase to repress gene transcription. Here, we identify the protein phosphatase 1 (PP1), Glc7 as the enzyme that specifically dephosphorylates H3T11. We also characterize two novel Glc7-containing complexes and reveal their roles in regulating gene expression upon glucose starvation. Specifically, the Glc7–Sen1 complex dephosphorylates H3T11 to activate the transcription of autophagy-related genes. The Glc7–Rif1–Rap1 complex dephosphorylates H3T11 to derepress the transcription of telomere-proximal genes. Upon glucose starvation, Glc7 expression is up-regulated and more Glc7 translocates into the nucleus to dephosphorylate H3T11, leading to induction of autophagy and derepressed transcription of telomere-proximal genes. Furthermore, the functions of PP1/ Glc7 and the two Glc7-containing complexes are conserved in mammals to regulate autophagy and telomere structure. Collectively, our results reveal a novel mechanism that regulate gene expression and chromatin structure in response to glucose availability

Clinical Research of EGFR and KRAS Mutation in Fine Needle Aspiration Cytology Specimens of Non-small Cell Lung Carcinoma

Background and objective Epidermal growth factor receptor (EGFR) and KRAS must be detected mutation status before patients of lung cancer use targeted drugs. The aim of this study is to elucidate the significance of EGFR and KRAS mutation in fine needle aspiration (FNA) cytology suspension specimens of non-small cell lung carcinoma. Methods EGFR gene exons 18-21 and KRAS codons 12, 13 of exons 2 were performed by Real-time PCR methods in fine needle aspiration cytology suspension specimens of lymph nodes. Results 85 metastasis lymph nodes were detected in fine needle aspiration cytology samples of lung cancer. EGFR mutation rate was 37.3%. KRAS mutation rate was 7.2%. 19 formalin fixed paraffin-embedded tissue specimens were available and match cytology specimens. Analysis of EGFR mutation status in those samples revealed agreement with the results obtained in cytological samples (kappa=1.0). Clinical follow-up was available for 13 who presented with stage IV disease. Based on the identification of such mutations, these patients received subsequent therapy with a TKI in clinic. We observed two cases complete remission (16.7%) and 8 cases partial remission (66.7%) and three had ongoing stable disease. Conclusion Fine-needle aspiration cytology samples were detected EGFR and KRAS mutation. The method which collects samples was easier, simple and convenient. This method has higher application value in clinical treatment

Myeloid Leukemia Factor Acts in a Chaperone Complex to Regulate Transcription Factor Stability and Gene Expression

Mutations that affect myelodysplasia/myeloid leukemia factor (MLF) proteins are associated with leukemia and several other cancers. However, with no strong homology to other proteins of known function, the role of MLF proteins in the cell has remained elusive. Here, we describe a proteomics approach that identifies MLF as a member of a nuclear chaperone complex containing a DnaJ protein, BCL2-associated anthanogene 2, and Hsc70. This complex associates with chromatin and regulates the expression of target genes. The MLF complex is bound to sites of nucleosome depletion and sites containing active chromatin marks (e.g., H3K4me3 and H3K4me1). Hence, MLF binding is enriched at promoters and enhancers. Additionally, the MLF-chaperone complex functions to regulate transcription factor stability, including the RUNX transcription factor involved in hematopoiesis. Although Hsc70 and other co-chaperones have been shown to play a role in nuclear translocation of a variety of proteins including transcription factors, our findings suggest that MLF and the associated co-chaperones play a direct role in modulating gene transcription

The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts

Megakaryocytes (MKs), a kind of functional hematopoietic stem cell, form platelets to maintain platelet balance through cell differentiation and maturation. In recent years, the incidence of blood diseases such as thrombocytopenia has increased, but these diseases cannot be fundamentally solved. The platelets produced by MKs can treat thrombocytopenia-associated diseases in the body, and myeloid differentiation induced by MKs has the potential to improve myelosuppression and erythroleukemia. Currently, ethnomedicine is extensively used in the clinical treatment of blood diseases, and the recent literature has reported that many phytomedicines can improve the disease status through MK differentiation. This paper reviewed the effects of botanical drugs on megakaryocytic differentiation covering the period 1994–2022, and information was obtained from PubMed, Web of Science and Google Scholar. In conclusions, we summarized the role and molecular mechanism of many typical botanical drugs in promoting megakaryocyte differentiation in vivo, providing evidence as much as possible for botanical drugs treating thrombocytopenia and other related diseases in the future

Enrichment of DNA sequences that bind to AGR2-GST-beads.

<p>a) Flow cytometry assay to monitor the binding of a selected pool with AGR2 (target protein) and GST (control protein). The red curve represents the background binding of unselected library. For the target protein AGR2, there was an increase in binding capacity of the pool as the selection progressed, while there was no observable change for the control protein GST. The final concentration of the selected pool in binding buffer was 100 nM. b) Determination of the dissociation constant of the enriched library and unselected library to AGR2. c) Fluorescence measurements to determine the dissociation constant of selected aptamer C14B. Two negative controls, GST-beads and GSH-beads, were carried out. The data were the average of triplicate experiment results.</p