Abstract:Heterogeneity is an important feature of malignant tumor. It could appear as diversity from genotypes to phenotypes in different patients with the same type of cancer or different parts of tumor biopsies in a single cancer patient. The heterogeneity could appear in diverse genetic backgrounds, pathological patterns, differentiation stages, genetic mutation spectrum, transcriptomics and proteomics gene expression profile, etc, which indicate the high complexity and diversity in cancer progression. Tumor heterogeneity is a great challenge of cancer treatment, and is also an important research field of tumorigenesis. In this paper, we reviewed the biological features of tumor heterogeneity and possible mechanisms of its occurrence, and gave our considerations on how to design more effective personalized treatment that aims tumor heterogeneity in the era of "precision medicine".

Abstract:With the rapid development of high-throughput sequencing technologies, the emerging of methylated RNA immunoprecipitation sequencing (MeRIP-seq) technology makes it possible to detect RNA epigenetic modifications in a large scale, which allows transcriptome-wide profiling of RNA methylation. Mining the patterns of global mRNA methylation from these MeRIP-seq data can help reveal the potential functional roles of these mRNA methylations in regulating gene expression, splicing, RNA editing and RNA stability, effectively guiding the therapeutic intervention of cancer. Here, the principle of MeRIP-seq sequencing was first introduced. Then, the recent progress of the processing and analysis of MeRIP-seq data were comprehensively discussed. In the end, the computational problems and challenges faced in the process of MeRIP-seq data processing were also summarized.

Abstract:The issue about when cognitive aging onset has been a hot point both in aging psychology and gerontology. The answer to this question is critical in determining the optimum time of cognitive intervention. According to three large scale longitudinal studies (Seattle Longitudinal Study, Betula Project, Virginia Cognitive Aging Project), longitudinal studies show that the onset of average decline in cognitive abilities occurs at considerably later ages (e.g. age 50～60) than that suggested by cross-sectional studies (e.g. age 20～30). Moreover, the debate of onset of cognitive decline was discussed from the perspective of quasi-longitudinal，which reveals nearly monotonic declines in cognitive performance from early adulthood. However, the answer for the timing of cognitive decline is elusive now. Future research on the timing of cognitive aging should clarify the methods, and combine the neurobiological study in the cognitive performance.

Abstract:Animal guts are constantly exposed to various ingested microbes that trigger immune response. Prolonged infection causes gastrointestinal diseases in human. The Drosophila midgut has emerged as a useful model to study the homeostasis maintained by resident intestinal stem cells (ISCs) and their progeny, creating an active research field with prolific publications. In this study, we make a summing up of relevant researches of the mechanisms on the proliferation and differentiation of ISCs, meanwhile, we look far ahead into the prospect in this field, which make the theoretical base of the research for gut homeostasis in Drosophila.

Abstract:NF-E2-related factor-2(Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. Oxidative stress could represent a common link between different forms of diseases. Nrf2 activation is initiated by oxidative or electrophilic stress, and induces its target genes by binding to the antioxidant response element (ARE)aimed at cytoprotection. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis,drug-induced liver injury,alcoholic and nonalcoholic liver disease and cancer via target gene expression. The relevant literatures concerning the role of the Nrf2 and its pathway in protecting against hepatic injury were summarized and we will discuss the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.

Abstract:UBXD8 is a membrane protein that mediates endoplasmic reticulum-associated protein ubiquitination and degradation by interacting with p97/VCP. Recently, lipid droplet proteomic studies show the lipid droplet localization of UBXD8. Besides, UBXD8 is also involved in triglyceride metabolism. However, the molecular mechanism by which UBXD8 regulates triglyceride metabolism is still obscure. Here we knocked out UBXD8 in mouse C2C12 myoblasts by CRISPR/Cas9. We selected 2 UBXD8 knockout (KO) clone cell lines from 26 possible KO clones. UBXD8 KO did not change the lipid droplet proteins expression pattern. However, UBXD8 KO led to the accumulation of neutral lipid. Furthermore, our data show that UBXD8 KO could alleviate palmitate-induced insulin resistance and rescue palmitate-induced apoptosis which was characterized by PARP splicing. In addition, the phenotype of palmitate-induced insulin resistance and apoptosis was reappeared after overexpressing UBXD8 in UBXD8 KO cells. These data suggested that UBXD8 plays an important role in lipid metabolism and its abnormity related insulin signal and apoptosis.

Abstract:MutM (Formamidopyrimidine-DNA glycosylase, Fpg), a bifunctional base excision repair enzyme (DNA glycosylase/AP lyase), is involved in the repair of many kinds of DNA damage, including the formation of 8-oxoguanine, 5-formyluracil, and C/C mismatches, through recognizing DNA damage and removing damaged bases. The mechanisms of MutM involvement, however, with the exception of 8-oxoG, are poorly understood. Here, we identified proteins which interact with MutM in Mycobacterium smegmatis using methods of tandem affinity purification and mass spectrometry and used Far-western and GST pull-down analysis to validate the interactions between MutM and DEAD-box rna helicase, RpsC, and UvrA. Results demonstrated that tandem affinity purification is a suitable method for identifying MutM interacting proteins and provided insights into the mechanism by which MutM is involved in DNA damage repair.

Abstract:Postherpetic Neuralgia (PHN) is a kind of chronic refractory neuropathic pain, yet there is a lack of knowledge regarding underlying brain activity. To further investigate brain activity changes in patients with PHN, we used amplitude of low frequency fluctuation (ALFF) analysis of resting-state fMRI to observe basal brain activity in those patients. Resting-state fMRI acquired in 8 PHN patients as well as in 8 age- and sex-matched normal controls was compared. Voxel-based multiple regression analysis was performed by SPM8 with voxel-wised ALFF as dependent variable, VAS score and pain duration as a covariate of interest. Comparing with healthy controls, PHN showed significant ALFF increases associated with VAS score in right cerebellum posterior lobe, dorsolateral prefrontal cortex (BA11/46/47), right parietal lobe (BA40) and right lingual gyrus(BA17/18/19); significant ALFF decreases associated with VAS score in right middle temporal gyrus(BA21), left lingual gyrus(BA17/18), right cerebellum anterior lobe, left posterior cingulate(BA30/19) and right precentral gyrus(BA3/4/6); significant ALFF increases associated with pain duration in right cerebellum posterior lobe, right middle frontal gyrus, dorsolateral prefrontal cortex(BA9/10/11/47), left superior temporal gyrus (BA38), right parietal lobe and right lingual gyrus (BA17/18/19); significant ALFF decreases associated with pain duration in left parahippocampa Gyrus (BA28), right cerebellum anterior lobe, left cingulate gyrus (BA24), right superior temporal gyrus (BA13), left precentral gyrus and right inferior parietal lobule (BA39/40). The results suggested that the brain areas involved in emotion, attention of pain played an important role in the modulation of PHN.

Abstract:Based on the Purkinje system and the anatomically detailed ventricular geometry of a human heart, an integrated 3D human ventricular conduction model is proposed to simulate the reentry wave propagation for studying the generation mechanism of ventricular fibrillation caused by early afterdepolarizations. This model was simulated the cardiac cell electrical activity of early afterdepolarizations and the susceptibility to early afterdepolarizations of three kinds of cells. Then, the influence of cells which is susceptibility to early afterdepolarizations on the reentrant spiral wave dynamics was analyzed. Finally the ECG waveform under ventricular fibrillation caused by early afterdepolarizations was quantified. The experimental results showed that the middle cells are most likely to generate early afterdepolarizations. With generating early afterdepolarizations in middle cells, the reentrant wave would be broken up and the ECG waveform would be disordered and irregular, which was in agreement with the results obtained on animal models. Therefore, it may be an important target for inducing ventricular fibrillation.

Abstract:Pregnancy complications, such as, recurrent pregnancy loss, gestational diabetes mellitus, preterm labor, intrauterine growth restriction and preeclampsia, greatly impaired the health and quality of daily life of pregnant women and neonatal. However, the etiology of most of the pregnancy complications is still unclear. Recently, appearing in younger population and increasing incidence of lipid and carbohydrate metabolism disorders, such as obesity and diabetes, will lead to increasing reproductive health issues in this population. Studies have shown that the pregnancy complications are correlated with lipid and carbohydrate metabolism disorders and hypertension, but the internal links are still unclear. Adipokine Chemerin was involved with both of the metabolism disorders and hypertension, so as abnormal expressed in pregnancy complications. However, whether it is the cause of pathogenesis of pregnancy complications or not, is still unclear. To address the possible etiological role of Chemerin with pregnancy complications, we summarized the research advance of Chemerin on pregnancy and pregnancy complications studies and combined with the findings in the pathogenesis of Chemerin with metabolism disorders and hypertension. This review will provide new ideas and directions for pregnancy complication investigations.

Abstract:Making concerted efforts to get a scientific break-through: A glance back at structure analysis of Artemisinin

Abstract:The DNA repair researchers were awarded by Nobel Commitee and Lasker Foundation in the same year

Abstract:The definition of consciousness can be described as "a brain basic function that an individual realizes oneself in a real world (environment)." This is to say, consciousness works for human to perceive the reality of oneself and the environment under wakefulness. The perception of the reality is a brain fundamental function for attention, learning, cognition and thinking, etc. So far, many scientific laboratories study human consciousness related with anesthesia because they attempt to reveal how consciousness works when brain reboots awareness. Recently, Solovey and colleagues (J Neurosci, 2015, 35(30): 10866) found that different anesthetics induce different patterns of brain activity. Loss of consciousness is universally and reliably associated with stabilization of cortical dynamics regardless of the specific activity characteristics.To give an analogy, their analyses suggest that loss of consciousness is akin to depressing the damper pedal on the piano, which makes the sounds dissipate quicker regardless of the specific melody being played. Here is a suggestion that the consciousness under the basic metabolism should be observed when a person just awake from asleep state, because s/he just realizes herself or himself in a real world, without disturbance from those of drugs for anesthesia of brain.