Abstract:In 2019, the Nobel Prize in Physiology or Medicine was awarded to William G.Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L.Semenza for their discoveries in mechanism of how cells sense and adapt to oxygen level. Hypoxia-inducible factor-1 (HIF-1) plays a key role in this mechanism. It can act as a transcription factor to alter gene expression and adapt to hypoxia by increasing oxygen carrying capacity, increasing blood supply, and changing metabolic patterns. The function of HIF-1 is also regulated by various mechanisms: ubiquitination-proteasome pathway degradation and inhibition of transcription factor activity under the action of tumor suppressor proteins pVHL, proline hydroxylase (PHD), factor inhibiting HIF (FIH), etc. This paper summarizes the research results of three Nobel Prize winners, and introduces the latest progress, systematically expounds the regulation mechanism of HIF-1 and HIF-1 mediated cell adaptation to hypoxia.

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Abstract:Glioblastoma is the most malignant form of brain tumors in adults. Therapeutic development has been stagnant for decades until recent years. With the advent of precision medicine and next generation sequencing, it is crucial to examine the complex mechanisms underlying this deadly disease for accurate prognostic prediction. Secondary or recurrent glioblastomas with matched initial tumors are invaluable cases to study, as they allow us to understand glioma progression over time and space with resistance to treatment. Here we review the complexities within glioblastomas, including a wide array of driver alterations, spatial heterogeneity and diverging evolutionary trajectories over time, and how these knowledge can facilitate prognostic prediction and therapeutic translation.

Abstract:tRNA-derived small RNAs (tsRNAs) is a type of newly discovered non-coding small RNA, which is derived from mature tRNA or tRNA precursor and exists in various organisms. tsRNAs exhibit tissue- and cell-specific expression and are involved in various biological functions such as stress response, protein translation regulation, ribosomes biogenesis, intergenerational transmission of acquired epigenetic information, tumorgenesis, cell proliferation and apoptosis. This review briefly discussed the biogenesis, classification, biological functions and molecular mechanisms of tsRNAs, as well as the roles of tsRNA modifications in tsRNA regulation and in diseases diagnosis.

Abstract:Exosome is a kind of micro and nanometer level extracellular vesicles. Because it can directly participate in the transmission of information between cells and the transport of substances, exosome is considered to be an important carrier of biomarkers for intercellular communication, immunomodulation, disease diagnosis and prognosis. In addition, the nucleic acid and protein contained in exosome can affect significantly the physiological state of recipient cells. As an endogenous non-coding microRNA, miRNA is of great value in the diagnosis and treatment of diseases. There is a great deal of evidence that these molecules play a role in controlling and regulating the pathogenesis of lung diseases. This review article focuses on the biological characteristics and functional fields of exosome derived miRNA in recent years, and summarizes the regulation function and mechanism of exosomal miRNA in lung diseases, especially pulmonary fibrosis, which is a hot topic in biomedical research in recent years. Therefore, it can not only act as a new molecular biomarker for the diagnosis of pulmonary fibrosis, but also suggest a new therapy strategy for exosomal intervention of pulmonary fibrosis.

Abstract:Early diagnosis of cancer can increase the survival rate of patients. Minimally invasive liquid biopsy can avoid the problems of invasion and heterogeneity of traditional tumor biopsy methods, also is becoming a new approach for cancer diagnosis. In addition, DNA methylation as a marker to predict the occurrence and development of cancer has aroused more and more researchers" interest. But the traditional DNA methylation detection methods usually possess poor sensitivity and false positive. In recent years, digital PCR technology has been used for quantitative detection of DNA methylation because of its super sensitivity, better accuracy and the advantage of absolute quantification of nucleic acids without standard curve. Firstly, this review introduced the relationship between DNA methylation and carcinogenesis, then summarized the traditional detection methods of DNA methylation and their applications in clinical cancer early diagnosis. Secondly, the digital PCR based on different methods of nucleic acid sample dispersion and its advantages in the detection of DNA methylation are elaborated. Also, this review summarized the specific steps of using digital PCR to detect DNA methylation in body fluids for cancer diagnosis. Finally, we reviewed the research results and application progress of digital PCR in cancer DNA methylation detection. The possible challenges in the future of digital PCR in cancer DNA methylation detection are put forward and the opportunity of digital PCR in cancer liquid biopsy are prospected.

Abstract:In bacterial DNA replication, DnaG primase synthesizes RNA primers which are then extended by DNA polymerase. The DnaG primase consists of three domains, N-terminal zinc-binding domain (ZBD), RNA polymerase domain (RPD) and C-terminal helicase binding domain (HBD). In the process of producing primers, the three domains of primase cooperate with each other, and none is dispensable. Although the structures of the primase domains have been reported, so far, the full-length structure of the primase is not known yet. Here, the model of full-length DnaG in Bacillus subtilis (BsuDnaG) was constructed from the data of X-ray small angle scattering (SAXS) analysis. The BsuDnaG is in extended state in solution. On the other hand, the ZBD and HBD domains could exhibit continuous conformational changes relative to the RPD domain. This study suggests the domains rearrangement in DnaG primase may facilitate its function in DNA replication.

Abstract:In this paper, a multi-exposure fusion high-motion projection tomography three-dimensional imaging method based on spatial frequency filtering is proposed to realize the three-dimensional structure imaging of living zebrafish(17 mm×4 mm, maximum thickness 2.33 mm, minimum thickness 0.29 mm). Our method is to record the series of absorption images by using different exposure time of the camera, transform each image into the frequency domain to remove the low frequency, and then superimpose each filtered spatial frequency signal and inverse Fourier transform back into the air domain, and the transformed image is normalized to obtain a high dynamic image. The high dynamic absorption projection image is obtained at each projection angle, and then reconstructed by a filtered back projection algorithm to obtain highly dynamic three-dimensional structure information. The experimental imaging results show that the multi-exposure fusion high-visibility optical projection tomography three-dimensional imaging study of spatial frequency filtering can obtain more abundant spatial information of complex structures, and the relationship and process of early embryo growth and development of zebrafish monitoring and quantitative assessment have certain application prospects.

Abstract:Alternative splicing is crucial for post-transcriptional regulation and is responsible for transcriptome and proteome diversity. In recent years, with the completion of transcriptome sequencing of plants such as Arabidopsis thaliana, Oryzasativa, and Maize, researchers found that pre-mRNA alternative splicing in plant is involved with tissue differentiation and development, etc. In this work, RNA-seq data was downloaded from GEO database. Trimmomatic, Salmon, DESeq2, SUPPA2 and other tools were employed to detect expression genes and alternative splicing events in seed, root, leaf, flower, pedicel, internode and pod across the Arabidopsis. Then, differentially expressed genes and differential alternative splicing events were identified throughout 7 tissues. Furthermore, the comparison between leaves and flowers was taken as an example to display the corresponding biological functions. In this study, the tissue specificity of gene expression and alternative splicingin Arabidopsis was systematically investigated. It’s helpful for elucidating gene expression mechanism in plant genome.