Abstract:The investigation about chromatin 3D structure is becoming one indispensable way in studying genome functions and gene regulation. In past several years, thanks to the development of chromatin conformation capture technology and decreasing cost of high throughput sequencing, the amount of whole-genome interaction data increases rapidly with the ascending resolutions. This not only brought the chances for interpreting 3D genome, but also challenged the modeling methods. Nowadays, methods of analyzing these data covered a wide range, including pre-processing, normalization, visualization, features extraction and 3D modeling; however, choosing efficient and precise computational methods becomes an obstacle limiting the study of 3D genome. In this paper, we sum up these methods according to their suitable conditions, principles and characters and focus on the methods for new technologies and requirements in order to promote the application and development of these methods, assisting the investigation of 3D genome.

Abstract:The advent of atomic force microscopy (AFM) provides a powerful tool for probing the physical properties of native biological samples with unprecedented spatiotemporal resolution at the micro/nanoscale, significantly complementing traditional biochemical assays. In recent years, multiparametric imaging AFM, which is able to simultaneously obtain the topographical features and multiple mechanical properties (e.g., Young’s modulus, adhesion, and deformation) of biological samples, emerges as a new method for investigating the correlations between structure, mechanics and functions of biological systems. The biomedical applications of multiparametric imaging AFM have yielded considerable novel insights into cellular/molecular activities and the underlying mechanisms guiding pathological processes. In this paper, based on our own research in single-cell detection using AFM, the principle of multiparametric imaging AFM is presented and the progress in utilizing multiparametric imaging AFM to probe cellular and molecular mechanics is summarized. The challenges and future directions are also discussed.

Abstract:Autophagy is an evolutionarily conserved cellular degradation program. Abnormalities in autophagy are directly linked to human ailments. In the cardiovascular system, autophagy is essential for maintaining normal contraction and conduction at low basal levels under physiological conditions. Meanwhile, under pathological conditions, such as ischemia/reperfusion injury and heart failure, autophagy is enhanced. Accumulating evidence shows that microRNA plays a crucial role in autophagy in the cardiovascular system, including cardiac development, maintenance of normal physiological functions, and in different cardiovascular diseases (CVDs). In this review, we highlight the recent advances in the understanding of the relationship between microRNAs and the related autophagic regulation in CVDs. It is expected to provide a new direction for the diagnosis and therapy of CVDs.

Abstract:Long non-coding RNA (lncRNA) is involved in various physiological and pathological processes of tumors. Studies have shown that lncRNAs can participate in gene expression regulation by interacting with microRNA (miRNA) response elements (MREs) and forming a competitive endogenous RNA (ceRNA) regulatory network with other RNA molecules. The lncRNA plays an important role in non-small cell lung cancer (NSCLC) development via ceRNA function. It provides valuable insights into the molecular mechanism of NSCLC and novel targets for precision medicine of NSCLC. This review is based on our previous discovery of lung cancer-related ceRNAs and focuses on the role of lncRNA by acting as highly/lowly expressed and therapeutic ceRNAs in NSCLC.

Abstract:With the rapid development of epigenetics, there has been increasing concern with Lamarck’s theory of evolution which shed light on the inheritance of acquired characteristics. In recent years, transgenerational inheritance of mammalian acquired characteristics has also been investigated in detail. Epigenetic information, induced by environmental stresses, is transmitted through the germline during transgenerational inheritance of mammalian acquired characteristics. Spermatozoal sncRNAs play a key role in the establishment of epigenetic information which is associated with environmental stresses and function during transmission of epigenetic information．The environmental stresses related epigenetic information, embodied in sncRNAs, is stored in the mature spermatozoa．Subsequently, spermatozoal sncRNAs is involved in epigenetic modification in primordial germ cells after fertilization. Then these epigenetic modifications can be transmitted between generations, thereby affecting the expression of genes which are associated with acquired characteristics. In this paper, we review the mechanism through which spermatozoal sncRNAs participate in transgenerational inheritance of mammalian acquired characteristics, providing new ideas to investigate hereditary metabolic diseases or to promote human reproductive health and livestock breeding.

Abstract:Pluripotent stem cells (PSCs) hold unlimited proliferation ability and the potential to generate cardiomyocytes, providing new sources of cells for heart regeneration. Development biology provides important clues for directed differentiation. During the past few years, great progresses on cardiomyocyte differentiation have been made by manipulating cardiac developmental pathways. However, the protocol for directed cardiomyocyte differentiation is not reproductive between cell lines, indicating that current pathways are not efficient enough. Retinoic acid (RA) pathway deficiency in embryo results in severe heart development abnormalities, including impaired atria development, reduced trabeculae, thickened myocardium and loosely attached cells in ventricle. During directed cardiomyocyte differentiation, RA were mainly used for atrial cardiomyocytes induction from pluripotent stem cells. However, based on the phenotypes of RA pathway knockout mice, the function of RA is not limited to cardiac subtypes specification. Exploring the mechanisms of RA on different stages of cardiac differentiation will contribute to directed differentiation of cardiomyocyte. Meanwhile, clarifying the mechanisms of RA in endocardial and epicardial differentiation will explain the impaired heart development of RA deficiency. In conclusion, according to the functions of RA in heart development, more in vitro studies on cardiac lineages differentiation should be performed to uncover the mechanisms of RA. Here, we reviewed the functions of RA in cardiac development and cardiomyocyte differentiation, and discussed the issues need to be solved further.

Abstract:The synthesis, antibacterial activity and mechanism of Yb³⁺-Catechin complex (Yb³⁺-C) were systematically studied in this work. The experimental results showed that the optimum coordination mole ratio of Yb³⁺-C was 1∶4. The minimum inhibitory concentration (MIC) of Yb³⁺-C was significantly lower than that of single Yb³⁺ and C. Yb³⁺-C exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella, and more effective for Staphylococcus aureus and the MIC value was only 0.0963 mmol/L. Further investigation showed that the sterilization time of Yb³⁺-C was greatly reduced to 2 h. In addition, the analysis of scanning electron micrograph (SEM), transmission electron microscope (TEM), and adsorption and distribution of Yb³⁺ in cell membranes and intracellular indicated the stronger affinity and penetration ability of Yb³⁺-C to bacterial cells. Therefore, the Yb³⁺ in the form of Yb³⁺-C is more easily accumulated to the effective concentration in the cytoplasm, resulting the damage of cellular structure and apoptosis.

Abstract:The detection of nuclear acid polymorphism has an important role in basic research and clinical application. The popular methods are PCR based on probe. Probe with cross-reactivity limits the application of traditional real-time quantitative PCR to quantitate allelic transcripts．Digital (d)PCR may overcome cross-reactivity defects, but available dPCR machines lack discrete optical channels, which limits the detection of more than two molecules. Colon cancer associated transcript 2 (CCAT2) is a non-coding transcript, encompassing rs6983267 SNP site. Here, we report a method based on two channels droplet digital PCR to quantitate three CCAT2 polymorphisms in one reaction. We designed a pair of primers and three hydrolysis probes including a reference and two competing probes. We successfully discriminated between the three CCAT2 transcript clusters. We took advantage of the cross-reactivity to provide a white space for more visible distinct clusters, although innate rain was detected. Labelling the reference probe with cross-reactivity probe resulted in more distinct clusters than the probe without cross-reactivity.

Abstract:Fluorescence correlation spectroscopy (FCS) technologies have the advantage of ultrasensitivity (single molecule), fast speed (seconds and minutes measurement time), and multifunctionality (simultaneously analyzing molecular concentration, size and interaction).Thus, FCS technologies have the potential of being a novel fluorescence immunoassay suitable for high-sensitivity analysis of homogeneous sample solution. This article introduces the principles and applications of FCS technologies based on the reliable, easy-to-use, bench-top fluorescence correlation spectrometer developed by the project team.

Abstract:The 2018 Nobel Prize in Physiology or Medicine was awarded jointly to James P. Allison and Tasuku Honjo for their contributions to cancer therapy by inhibition of negative immune regulation. This discovery sheds new light on immunotherapy. In this paper we reviewed the research on CTLA-4 and PD-1, two well-studied immune checkpoints. We also investigated the drug development and clinical use which are targeted to immune checkpoint, as well as the development of immunotherapy in China. Meanwhile, we discussed the limitations in immunotherapy at present and the solutions to solve the problem of adverse effects existed in immunotherapy. China has made great progress in the research of immunotherapy because of the young talents coming back to China and the excellent research platforms as well as the great investment in the field of immunotherapy in recent years. There is no doubt that the immune checkpoint inhibitors developed by China will be accepted globally and China will make great contributions to the cancer therapy in the near future.