Abstract:Minichromosome maintenance (MCM) proteins are key elements that function as a part of the pre-replication complex to initiate DNA replication. Individual MCM proteins also help to regulate transcription, chromatin remodeling and check point responses. Recent studies indicated that MCM expression is abnormal in many tumors (prostate cancer, endometrial cancer, ovarian cancer, liver cancer, lung cancer, glioblastoma, medulloblastoma, etc.), and is associated with the abilities of proliferation, invasion, metastasis in tumor. Clinical studies have shown that MCM proteins are indicators of tumor proliferation and poor prognosis, and are also identified as potential targets for new treatments of cancers. With the discovery of the crystal structure of the MCM protein complex, the underlying mechanism of MCMs, especially those in the tumors, will be further elucidated. It will also help to develop novel small specific molecule inhibitors for targeting MCMs.

Abstract:In recent years, CRISPR/Cas9 system has rapidly become the most revolutionary gene editing tool in the field of medicine. It is the third-generation artificial endonuclease after Zinc-finger nucleases (ZFNs) and transcription activator-like effectors nucleases (TALENs), and is known as "gene scissors". CRISPR/Cas9 system relies on a synthetic single guided RNA (sg RNA) to direct Cas9 nuclease to cleave the target DNA sequence, so that it can complete genomic site editing. Based on the simplicity of design, rapid implementation, low cost and high efficiency, CRISPR/Cas9 system has been extensively studied in the fields of gene functional identification, antiviral therapy, anti-tumor therapy and immunotherapy. Although CRISPR/Cas9 system displays several obvious advantages, the risk of off-target would increase the therapeutic risks, hinder research and clinical application, which should not be ignored. How to reduce the off-target effects and increase mutation efficiency simultaneously as we use CRISPR/Cas9 gene editing technology? This will be an urgent problem for scientists to explore CRISPR/Cas9 technology and expand its clinical application in the future. Here, we briefly introduce the composition, mechanism and application of CRISPR/Cas9 system, and give a comprehensive introduction of the off-target effect which is widely concerned in this field at present, and summarize the optimization strategies to provide references for researchers.

Abstract:Thermal strain imaging (TSI) is an ultrasound application which exploits the temperature dependence of ultrasonic echo time shift to form thermal strain images. The basic principle of TSI for medical examinations is that tissue expands and ultrasonic propagation speed changes when the temperature in tissue raises by using a directed-energy source to heat, causing relative shifts in scatterer position. The local temporal gradient of scatterer shift is often called thermal strain and thermal strain images are formed by measuring and restructuring thermal strain. In order to optimize the energy transfer and heating efficiency, a highly controllable energy source is a critical part of the TSI system. Ultrasound is the dominant energy source because it is noninvasive, nonradiative and can greatly simplify the probe design and its integration with existing scanners. As thermal strain is closely related to tissue components and temperature, the applications of TSI in biomedical field are mainly focused on tissue characterization and temperature monitoring. Although the application of TSI has been extensively studied, TSI currently can not be applied in clinical trials mainly due to the obstruction of tissue motion. To reduce negative effects of tissue motion, various methods for motion compensation have been attempted and good results have been achieved. We have reasons to believe that TSI will be generally welcomed as a new noninvasive clinical application with the improvement of energy source and the appearance of more effective motion compensation methods.

Abstract:Upconversion luminescent nanomaterials have the significant advantages of long fluorescence lifetime, low potential biotoxicity, large penetration depth, small damage to biological tissues and few background light. In recent years, photodynamic therapy, bioimaging and biological detection have been widely used, but in the process of application, there are some problems such as low efficiency of energy transfer between UCNPs and target, overheating of normal tissues. In biological imaging, the fluorescence intensity is weak, the photosensitizer and activator have energy reflow, and the imaging mode is single. Researchers have developed a lot of solutions to these problems, such as shortening the distance between UCNPs and targets, changing the intensity of laser irradiation and the structure of UCPs, integrating UCNPs as a new multifunctional platform for imaging and treatment, etc., so that some of the problems are well solved. This review focuses on the solutions to the problems that arised from the use of UCNPs in PDT and bioimaging. The future development of UCNPs in biomedicine is also discussed.

Abstract:Cell wall proteins (CWPs) play very important roles in cell metabolism and developmental regulation, modification of cell wall constitutes, signaling transduction, stress response and other biological events in plants. Recently, the domestic and foreign researchers have developed various studies underling proteomics profiling of plant CWPs and achieved great advance. This review describes the latest research progress of plant CWPs in the classification, extraction, identification and bioinformatics analyses, summarizes the utilization and facing challenge of plant cell wall proteome, and proposes a work model underline proteomics profiling of plant cell walls, which will be useful for the deep study on plant cell wall proteome.

Abstract:Postherpetic neuralgia (PHN) is a common type of neuropathic pain, the central mechanism of which is still unclear. The amygdala has recently garnered increased attention in pain processing. The purpose of this study is to investigate the functional neural networks of the amygdala in PHN and explore the mechanism of chronic neuropathic pain. Conventional magnetic resonance imaging (MRI) and resting-state functional MRI (fMRI) were performed in eight PHN patients and eight healthy controls. The functional connectivity (FC) of each subregion of the amygdala with the whole brain was computed. Paired t tests of the FC data were performed between the two experimental groups. Correlation analysis was applied between disease duration, visual analog scale (VAS), and FC strength. We found increased FC between the laterobasal (LB) and superficial (SF) amygdala and several brain regions including the temporal lobe and frontal lobe. We observed decreased FC between the SF amygdala and the precentral cortex, as well as the SF amygdala and parietal lobe. Correlation analysis showed that FC strength of the LB amygdala with both the temporal lobe and frontal lobe changed with disease duration and VAS in PHN patients. This altered FC in PHN suggests that the amygdala and several other brain regions involved in emotion, recognition, and attention play an important role in the modulation of chronic neuropathic pain.

Abstract:The global rise of obesity and obesity-associated complications such as type 2 diabetes and cardiovascular disease has become a major public health concern. The etiology and pathogenesis of these obesity- related diseases are caused by multiple factors, and the free fatty acid receptors may play important roles. G protein coupled receptor 84 (GPR84) is a medium-chain (C9-C14) fatty acid-sensing receptor. However, its functions in obesity and metabolic diseases remain unclear. In this research, we established a high-fat diet induced obesity model in wild type and GPR84 knockout mice. Compared with WT mice, GPR84 knockout mice have similar levels of food intake, body weight, oral glucose tolerance test and insulin tolerance test both on normal chow diet and high-fat diet. GPR84 deficiency in mice did not affect fasting blood glucose level, insulin, triglyceride, low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c). There were no genotypic differences in tissue mass, lipid synthesis, fatty acid oxidation and lipogenesis in mice on normal chow diet or high-fat diet. However, the concentration of total cholesterols (TC) was significantly reduced and scavenger receptor class B typeⅠ(SR-BⅠ) was significantly increased in GPR84 knockout mice compared with WT mice on high-fat diet. These results indicate that GPR84 may not be involved in glucose and lipid metabolism in mice; instead, it may play a role in hypercholesterolemia caused by high cholesterol.

Abstract:Endogenous H₂S was recognized recently as a new gaseous signaling molecule which plays beneficial roles in vasodilation and facilitation of long-term potentiation. The interaction of mammalian myoglobin (Mb) with H₂S occurs via two distinct pathways: the first is the direct binding of H₂S to the heme-Fe center of the Mb to form the Mb-H₂S adduct, and the second is the covalent modification with H₂S at a porphyrin vinyl group of the Mb heme to form the covalently modified sulfheme. We chose Mb as the prototype heme-containing protein and probed the interactions of different Mb mutants with H₂S by UV-vis spectroscopy, and X-ray crystallography. The heme active sites of Mb mutants directly affect the binding of H₂S to the proteins and alsothe formation of sulfheme derivatives. This provides critical experimental data for elucidating how heme-containing proteins modify the metabolism of endogenous H₂S.