block-preconditioned-pagerank-for-centrality-intervention-analysis

Block-Preconditioned PageRank for Centrality and Intervention Analysis In Commercial Networks

Commercial networks are shaped by heterogeneous drivers (e.g., geography, category structure, and operating performance), so a single financial indicator ...

Jiangsu Normal University

Long non-coding RNAs (lncRNAs) perform crucial roles in biological process involving complex mechanisms. However, information regarding their abundance, characteristics and potential functions linked to fish skin color is limited. Herein, Illumina sequencing and bioinformatics were conducted on black, white, and red skin of Koi carp (Cyprinus carpio L.).

Integrated analysis of long non-coding RNA and mRNA expression in different colored skin of koi carp.

Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening.

MicroRNAs (miRNAs) are ∼22 nucleotide non-coding RNA molecules that act as crucial roles in plenty of biological processes. However, the molecular and cellular mechanisms of miRNAs to regulate skin color differentiation and pigmentation in fish have not been fully understood. Herein, we revealed that miR-206, a skin-enriched miRNA, regulates melanocortin 1 receptor (, a key regulator of melanogenesis) expression by binding to its 3'-untranslated (UTR) region through bioinformatics and luciferase reporter assay in koi carp ( L.). The analysis of spatial and temporal expression patterns suggested that miR-206 is a potential regulator in the skin pigmentation process. Then, we silenced it  with an antagomir method. The result showed a substantial increase of  mRNA expression and protein level, and also its downstream genes: tyrosinase () and dopachrome tautomerase () that encoding key enzymes involved in melanin synthesis. Moreover, we constructed the miRNA-206 sponge lentivirus vector to transfect koi carp melanocytes , further checked the functions of melanocytes using Cck-8 and Transwell assays. As a result, inhibition of miR-206 significantly up-regulated  mRNA expression and protein level and accelerated the melanocyte proliferation and migration ability compared with the scrambled-sequence negative control group (miR-NC). Overall, these findings provide the evidence that miR-206 plays a regulatory role in the skin color pigmentation through targeting the  gene and would facilitate understanding the molecular regulatory mechanisms underlying miRNA-mediated skin color pigmentation in koi carp.

MicroRNA-206 Regulation of Skin Pigmentation in Koi Carp ( L.).

Bromodomain and extraterminal domain (BET) family proteins are considered to be epigenetic readers that regulate gene expression by recognizing acetyl lysine residues on histones and nonhistone chromatin factors and have been classified as curative targets for a variety of cancers. Glioma-initiating cells (GICs), which commit self-renewal, perpetual proliferation, multidirectional differentiation, and vigorous tumorigenicity, sustain the peculiar genetic and epigenetic diversification in the GBM patients, thus, GICs result in tumor recurrence. Abundant evidence demonstrates that BET proteins regulate differentiation of stem cells. However, it endures ambiguous how individual BET proteins take part in GIC advancement, and how do small molecule inhibitors like I-BET151 target functional autonomous BET proteins. Here, we validated that BRD4, not BRD2 or BRD3, has value in targeted glioma therapy. We announce a signaling pathway concerning BRD4 and Notch1 that sustains the self-renewal of GICs. Moreover, in-depth mechanistic research showed that BRD4 was concentrated at the promoter region of Notch1 and may be involved in the process of tumor metabolism. Furthermore, in intracranial models, I-BET151 eliminated U87 GICs' tumorigenicity. The outcomes of this research could be conducive to design clinical trials for treatment of glioma based on BRD4.

BRD4 regulates self-renewal ability and tumorigenicity of glioma-initiating cells by enrichment in the Notch1 promoter region.

Glioma is a primary cerebral neoplasm that originates from glial tissue and spreads to the central nervous system. Long noncoding RNAs are known to play a role in glioma cells by regulating cell proliferation, migration and invasion. The aim of the present study was to investigate the mechanism by which long intergenic non‑protein coding RNA (LINC) 01138 affects glycolysis and proliferation in glioma cells via the microRNA (miR)‑375/specificity protein 1 (SP1) axis. LINC01138 expression was assessed in glioma tissues and cells using reverse transcription‑quantitative PCR and the association between LINC01138 and patient clinicopathological features was analyzed. Glucose uptake, lactic acid secretion, cell proliferation, and glycolysis‑related enzyme levels were detected following LINC01138 silencing using CCK‑8, EDU assay and western blot analysis. miR‑375 and SP1 expression levels were also assessed, and the distribution of LINC01138 in the nucleus and cytoplasm was investigated using subcellular fractionation localization. Furthermore, the binding relationships between LINC01138 and miR‑375, and between miR‑375 and SP1 were assessed via dual‑luciferase experiment, RIP and RNA pull‑down assays. Finally, xenograft transplantation models were used to verify the  results. LINC01138 was highly expressed in glioma, which was independent of patient sex or age but was significantly related to tumor diameter, the World Health Organization tumor grade and lymph node metastasis. Silencing LINC01138 significantly reduced glioma glycolysis and cell proliferation. Moreover, LINC01138 acted as a competing endogenous RNA to sponge miR‑375 and promote SP1 expression. miR‑375 inhibition significantly reversed the effect of LINC01138 silencing. In addition, silencing LINC01138 significantly reduced tumor growth . The present study demonstrated that silencing LINC01138 inhibited aerobic glycolysis and thus reduced glioma cell proliferation, potentially by modulating the miR‑375/SP1 axis.

Article	Year
Integrated analysis of long non-coding RNA and mRNA expression in different colored skin of koi carp. BMC genomics\| PubMed ID: 31226932	2019
Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein & cell\| PubMed ID: 31919742	2020
MicroRNA-206 Regulation of Skin Pigmentation in Koi Carp ( L.). Frontiers in genetics\| PubMed ID: 32117457	2020
BRD4 regulates self-renewal ability and tumorigenicity of glioma-initiating cells by enrichment in the Notch1 promoter region. Clinical and translational medicine\| PubMed ID: 33135348	2020
Silencing long noncoding RNA LINC01138 inhibits aerobic glycolysis to reduce glioma cell proliferation by regulating the microRNA‑375/SP1 axis. Molecular medicine reports\| PubMed ID: 34643249	2021

Haoran Yin

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