Abstract:The Nobel Prize in Chemistry 2020 was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna "for the development of CRISPR genome editing tool." They have discovered the sharpest tools for gene editing: the CRISPR/Cas9 genetic scissors, which have revolutionary impact on life sciences. The CRISPR system is an adaptive immune system in prokaryotes. Cas9, an effector protein of type II CRISPR-Cas system, functions as a dual-RNA-guided DNA endonuclease, which is able to cleave any dsDNA generating dsDNA break. The CRISPR-Cas9 has been widely used in gene editing, due to its simplicity, high efficiency and low price. This paper introduces the research findings of 2020 Chemistry Nobel Prize winners, summarized the discovery process of CRISPR system and the activity and application of CRISPR-Cas9.

Abstract:In 2020, the Nobel Prize in Physiology or Medicine was awarded to Harvey J. Alter, Charles M. Rice and Michael Houghton for their discovery of Hepatitis C virus (HCV). Before the discovery of HCV, the research of Hepatitis A virus and Hepatitis B virus made an important breakthrough. However, a majority of blood-borne hepatitis belongs to non-A, non-B hepatitis, which was discovered as hepatitis C. The discovery of HCV makes blood transfusion safe and makes cure of hepatitis c become possible, saving millions of people’s life. By inducing chronic inflammation and other mechanisms, HCV invade hepatocytes, leading to liver cancer. This paper summarizes the biological characteristics of HCV, systematically expounds mechanisms of HCV infection-associated liver cancer, and introduces measures for prevention and cure of hepatitis c.

Abstract:Attention-Deficit/Hyperactivity Disorder (ADHD) and Developmental Dyslexia (DD) are two common neurodevelopmental disorders, the comorbidity rate of them is as high as 25% ~ 48%. In this paper, we reviewed and summarized the research progresses of ADHD comorbid with DD from multiple dimensions including cognitive psychology, neurophysiology (brain imaging) and molecular genetics. Three main theoretical models have been yielded for the neuropathological mechanisms of ADHD comorbid with DD, including phenocopy hypothesis, cognitive subtype hypotheses and common etiology hypothesis; whereas most of the evidence from the existing literature supported the common etiological hypothesis. Results in cognitive psychology indicated that the shared cognitive impairment in ADHD and DD might be the deficit of processing speed, which should be closely related to the comorbid status. The key imaging features related to ADHD comorbid with DDD might include the structural and functional alteration in frontal lobes (especially the dorsal lateral prefrontal cortex), caudate nucleus and anterior cingulate gyrus, and hemispheric asymmetry. For genetics, linkage studies suggested the potential association of the chromosome region of 6p21-22 with both ADHD and DD. In this region, two key genes, DCDC2 and KIAA0319, have attracted much attention and were studies as important candidate genes for ADHD and DD. Several other candidate genes would be also worthy of exploration to illustrate the common and shared genetic background of these two disorders, such as ADRA2A, DYX1C1, DRD4 may be related to the comorbidity of ADHD and DD. It is worth noting that the shared genetic factors of DD and ADHD may mainly affect the inattentive symptom and reading ability simultaneously, rather than hyperactive/impulsive symptoms. To further illustrate the neuropathologic mechanisms of ADHD comorbid with DD clearly and comprehensively, further multidimensional studies are needed to elucidate how the genetic susceptibility factors influence the brain structure and function, affect the cognition functions (eg. processing speed) subsequently and lead to the occurrence of ADHD clinical symptoms finally. Another important challenge should be addressed for the studies on ADHD comorbidity with DD. In China, most studies only recruited ADHD comorbidwith learning disabilities, which is mainly due to the lack of the standard clinical diagnosis criteria of Chinese DD. The establishment of a standard and unified diagnostic criteria for DD in Chinese background will promote the study progress and clinical intervention of ADHD comorbid with DD substantially.

Abstract:Eye gaze provides a type of crucial nonverbal cue that indicates other"s focus of attention, and hence gives rise to unique social attention behaviors. In recent years, it has been demonstrated that eye gaze cues can exert influences on the cognitive processing of general objects (e.g., tools or symbols) and those with social significance (e.g., faces). Using a modified social attention task, researchers have found that eye gaze cues can influence sensory perceptual processing, the liking ratings, memory performance and other high-level cognitive processing of gazed-at objects. Furthermore, such modulation of gaze cues on object processing can be mediated by the attributes and amount of the faces as well as the pattern of gaze shifts. More importantly, this modulation effect can occur in the absence of visual awareness and is highly specific to eye gaze but not non-social cues (e.g., arrow). Research probing the underlying mechanisms implied that high-level social cognitive abilities (i.e., theory of mind, perspective taking) might play a key role in the observed modulation effect. Yet to date, the exact mechanisms mediating this modulation effect remain an important question for further investigations. Future efforts concerning the mechanisms underlying the influences of gaze cues on object processing will help to extend our understandings of social functioning and the interaction between human and environment, and have implications for both theory construction and practical application.

Abstract:The replication and transcription machinery concurrently use the same DNA region as template so that the machineries inevitably collide with each other in the manner of either head-on or co-directional. Both head-on and co-directional collisions lead to a pause of replication fork, thereby DNA damage and genome instability. The head-on collision is more detrimental than the co-directional in respect of genome integrity. Here we review the resolving mechanisms and evolutionary impact of the replication-transcription collisions. The rate of nonsynonymous (amino-acid-changing) mutations on the lagging is higher relative to that on the leading strand and the high frequency mutagenesis in genes on the lagging strand is dependent on transcriptions and gene sizes, thus faster adaptive mutations occur on the lagging strand. Highly transcribing of head-on oriented genes increases the mutation rates responding to stress during active replication. It is likely that the replication-transcription collision no matter in the head-on or co-directional mode is a driving force for adaptive evolution.

Abstract:The long non-coding RNA (lncRNA) existing in the human genome has attracted much attention because of its important regulatory role. More and more studies indicated that lncRNAs play significant roles in neurodevelopment, neuroplasticity and central nervous system diseases. lncRNA nuclear enriched abundant transcript 1 (NEAT1) is abnormally expressed in the central nervous system diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), and is involved in important pathophysiological process. This article reviews the research progress of the NEAT1 in central nervous system diseases.

Abstract:Mitochondrial complex II, or succinate dehydrogenase (SDH), is regarded as a central regulator of respiratory adaptation and metabolic reprogramming in various stimuli and abnormalities. Four subunits of complex II are considered as tumor suppressors, whose mutations are associated with various type of cancer. However, little is known how complex II regulates cell proliferation. 2-Thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial complex II, and SDHB shRNA were used to abolish the activity of complex II in cell lines. Inhibition the activity of complex II by TTFA treatment or knockdown of SDHB could trigger mitochondrial fragmentation and subsequently mitophagy. We also found that inhibition of complex II also increased the glucose consumption and the lactate production which termed as Warburg effect. Despite of these, complex II dysfunction showed negative regulation to cell proliferation. Collectively, complex II is a potential target to induce mitophagy and inhibit cell proliferation.

Abstract:Objective :We performed directional differentiation of human embryonic stem cells into cardiomyocytes. In order to explore the mechanisms of cell metabolic phenotype conversion during cardiac lineage differentiation ,we conducted real-time quantitative detection of glycolytic and mitochondrial oxidative phosphorylation capabilities of embryonic stem cells, cardiac progenitor cells, and cardiomyocytes during differentiation. Methods: GSK3 inhibitor CHIR99021 and Wnt signaling pathway inhibitor IWP2 were used to differentiate human embryonic stem cells into cardiac progenitor cells and cardiomyocytes. Immunocytochemistry was used to detect the expression of human embryonic stem cell markers. Flow cytometry was used to detect the markers of human cardiomyocytes and cardiac progenitor cells. Extracellular Flux Analysis was used to test the energy metabolic phenotype of human embryonic stem cells, cardiac progenitor cells, and cardiomyocytes. Results: The stemness of human embryonic stem cells remains stable and all express Nanog, OCT4 and SOX2 cell markers. During the differentiation, more than 99% cells expressed cardiac progenitor cell marker Isl1 on the 7th day, and more than 83% of cells expressed the cardiomyocytes marker cTnT on the 15th day. Human embryonic stem cells have the strongest glycolytic metabolism capacity, while cardiomyocytes have the strongest mitochondrial oxidative phosphorylation capability. Cardiac progenitor cells are in the transition stage of the two ways of metabolism. Conclusion: During the differentiation of human embryonic stem cells into cardiomyocytes, cells gradually loss the glycolytic capacity, while the mitochondrial oxidative phosphorylation capacity gradually increases, followed by the cell metabolic phenotype conversion.

Abstract:Autosomal recessive primary microcephaly is a neurodevelopmental disorder associated with reduced brain size and intellectual disability. ASPM (abnormal spindle-like microcephaly-associated) is the most common recessive microcephaly gene, but the underlying mechanism is poorly understood. Here, we show that calmodulin function as a vital regulator of ASPM by interacting with its IQ-region. The complex of ASPM IQ-region and apo_calmodulin was purified and biochemically characterized with a 1:8 stoichiometry by size exclusion chromatography coupled with multi-angle static light scattering (SEC-MALS) and circular dichroism spectroscopy (CD). Interestingly, the binding ratio of ASPM IQ-region with Ca2+_calmodulin changed to 1:7 in the presence of Ca2+. In addition, by comparing the CD spectra with and without Ca2+, the ASPM-Calmodulin complex showed Ca2+-dependent thermal stability change. Taken together these results suggested a Ca2+-induced regulation mechanism of ASPM-calmodulin interaction.

Abstract:G protein-coupled receptors (GPCRs) mediate different cell transmembrane signal transduction, and are important drug targets. The β-arrestin mediated pathway is one of the important ways for GPCRs to play their function, which owns important significance for regulation of the function of GPCRs. However, until now it is still not clear how β-arrestin interacts with GPCRs and mediates their trans-membraned signal transduction pathway. To address this issue, the CC chemokine receptor 3 (CCR3) was selected to study the interaction between β-arrestin and GPCRs. Firstly, a co-expression system of β-arrestin and CCR3 was constructed, and the interaction between β-arrestin and CCR3 in living cells was analyzed using laser confocal fluorescence microscopy and fluorescence resonance energy transfer techniques. And the regulation effect of β-arrestin on the chemotaxis of CCR3 stably transfected cells was also studied by RNAi and chemotaxis experiments. In addition, the interaction between β-arrestin mutant (R169E) and CCR3 was further confirmed using QCM technology in vitro, and their binding constant was also determined. As a result, upon the stimulation of CCL11 (chemokine C-C motif ligand 11), the intracellular distance between β-arrestin and CCR3 was significantly changed, and β-arrestin protein was recruited to the cell membrane, which suggests that β-arrestin could interact with CCR3 and involve in the CCR3-mediated signal transduction process. After silencing β-arrestin by transfection with β-arrestin-siRNA, the migration of CCR3 stablely transfected cells induced by CCL11 and CCL24 was significantly decreased, while the migration rate induced by CCL5 was not obviously changed. These results indicated that different chemokines shows different regulatory effects on the interaction between CCR3 and β-arrestin. In vitro binding experiments further confirmed the interaction between β - arrestin and CCR3, and the binding constant KD between β - arrestin mutant and CCR3 was determined as 1.35 × 10-7. In conclusion, β-arrestin can interact with CCR3 in living cells, and plays an important role in CCR3-mediated cell transmembrane signal transduction.