Abstract:The efficient bioconversion of lignocelluloses is limited by the enzymatic hydrolysis efficiency, atomic force microscope (AFM) enables us to represent the Real-time motion behavior of the cellulase in the aqueous solution, to analysis the moving velocity and limiting factors. Cellobiohydrolase (CBH) is demonstrated to combine to specific site of the crystal face, to move unidirectionally and accomplish the degradation layer by layer. Over-dose cellobiohydrolase which combine to special face results in the "traffic jam" phenomenon. The degradation efficiency of crystal cellulose not only depends on the moving velocity of the enzyme molecule and the cleavage of glycosidic bond, but also lies on the crystal surface area of accessible substrate and the breakdown of hydrogen bonds on the crystal face. The novel cellulase complex or system with different combining mode, different movement mode or composition mode should be an important research aspect in the future.

Abstract:Methylation/demethylation of DNA, RNA and histone plays important roles in epigenetic functions. Formaldehyde is a significant factor participating in reversible and dynamic methylation of the biomacromolecules. As recently reported, memory formation and cognitive dysfunction are correlated with endogenous formaldehyde metabolism. Imbalance of formaldehyde metabolism affects DNA/RNA methylation and demethylation. Concentrations of endogenous formaldehyde are positively correlated with the severity of cognitive impairment of Alzheimer's patients in clinics. As an epidemiological survey shows, the levels of endogenous formaldehyde in elderly humans are negatively correlated with education years, suggesting that formaldehyde acts like a key factor in human learning and memory. "Live and learn" may mitigate the progression of age-related cognitive impairment resulted from imbalance of formaldehyde metabolism. Further investigation of endogenous formaldehyde involved in epigenetic modificaion and regulation should be carried out to understand the pathomechanism of cognition and cognitive impairment.

Abstract:Cyanobacteria are the simplest organisms with a confirmed circadian clock system. The pacemaker of cyanobacterial circadian clock is made of three proteins, KaiA, KaiB, and KaiC. A major finding on this system is that the circadian oscillation of the pacemaker system is independent of transcriptional/translational controls, and what is more intriguing is that this oscillation can be reconstituted in vitro with only these three proteins, in addition to ATP and an appropriate inorganic buffer. Molecular studies have shown that KaiA promotes the self-phosphorylation of KaiC, whereas KaiB antagonize KaiA's role and induce the de-phosphorylation of KaiC. An unsolved question is how KaiB interacts with KaiC exactly, including the binding site of KaiB on KaiC, the oligomerization form of KaiB, and the exact modulating mechanism of KaiB. Here, we reviewed the most recent progress on the KaiB-KaiC interaction mechanism, including our preliminary results on the KaiB-KaiC interaction, and provided a possible molecular mechanism of the molecular oscillator. We hope this review will provide a timely perspective on the study of this model system.

Abstract:Long noncoding RNA (lncRNA) play important roles in cancer progression. HOX transcript antisense RNA (HOTAIR) was observed upregulated in a variety of tumors. Over-expression of HOTAIR is a poor prognostic factor. HOTAIR interacts with Polycomb Repressive complex 2 (PRC2), resulting in histone H3 tri-methylated atlysine27 (H3K27me3), which silences the expression of some down-stream genes, such as WIF-1, PTEN and p21, then mediated Wnt, Akt and p53 signaling pathways transduction. As a result, the properties of tumor, including invasion and metastasis, evading growth suppressors, resisting apoptosis and inducing angiogenesis would be affected. Thoroughly elucidate mechanisms of HOTAIR in cancer development will have important theoretical significance in cancer etiology and pathogenesis. As an important biomarker and potential target, HOTAIR may also has important clinical application in cancer's early diagnosis, therapeutic evaluation, prognosis, and even potential gene therapy.

Abstract:The toxicity of anticancer drug limits its clinical applications, nano drug carriers which accumulate and release drugs at the lesion without affecting the normal tissue, can greatly improve the efficacy and reduced toxicity. Target ligands modified drug carrier can enhance active targeting ability, then release the drug into the target cells effectively. Aptamers are kind of nucleic acid molecules which could recognize and bind specific targets. They can be obtained by SELEX (systematic evolution of ligands by exponential enrichment) technology in vitro. Aptamers are widespread recognition, easy to modification and good stability, they are called chemical antibodies. As novel target molecules studied in recent years, aptamers have been used in targeted drug delivery. This review described several aptamer targeted drug delivery systems, such as aptamer-drugs, aptamer-liposomes, aptamer-polymer micelles, aptamer-polymeric nanoparticles, aptamer-metal particles and aptamer-branched polymer drug delivery systems. The existing problems and shortcomings of the research hotspots in the current study were also reviewed.

Abstract:Proteinase 3 is one of the major serine proteases secreted by neutrophils with multiple biological functions. It can degradate tissue proteins, process cytokines and receptors, thus contributing to the regulation of inflammatory and immune responses, and play important roles in the occurrence and development of chronic inflammatory diseases, such as granulomatosis with polyangiitis, chronic obstructive pulmonary diseases and pulmonoary fibrosis. In this reviews, we describle the biological functions of PR3 and its roles in human diseases, which might provide a new insight for the prevention and treatment of human diseases.

Abstract:YAP1(Yes-associated protein 1)is a molecular of Hippo pathway. In early studies, researchers found that YAP1 was inactive when Hippo pathway was well functional. When some molecules mutated in Hippo pathway, YAP1 was hyperactivated. Hyperactivated YAP1 could promote cell proliferation, metastasis, cell survival and maintain the activity of stem cell. Because hyperactivated YAP1 can promote the occurrence and progress of tumor, YAP1 was defined as an oncoprotein. Recently, researchers found that YAP1 variants were associated with survival rates of small-cell lung cancer patients. YAP1 interacted with catenin and Kras to regulate infiltration and metastasis of cancer cell. And some microRNAs could interact with YAP1. Based on the function of YAP1, we can find some therapeutic strategies and targets for cancer treatment. This paper summarize the studies of YAP1 and provide some evidence for basic and clinical research of cancer therapy.

Abstract:Acinetobacter baumannii is a new threat in intensive care units (ICUs) for its multiresistance to antibiotics, but little is known about this bacterium. Nucleoside diphosphate kinase (NDK) is an evolutionarily conserved enzyme that catalyzes phosphoryl transformation between nucleosides. In our study, the crystal structure of wild type Acinetobacter baumannii NDK along with its mutant generated through truncation of the C-terminal arginine-threonine-arginine (RTR) residues, were solved. In comparison with Myxococcus xanthus NDK structure, we speculated that Acinetobacter baumannii NDK shared a similar catalytic mechanism with Myxococcus xanthus. Activity assay and CD spectra analysis revealed that E28A mutant might interrupt the secondary structure of the protein leading to declined enzymatic activity. Truncation of the C-terminal RTR residues would lead to the instability of the tertiary structure resulting in reduced kinase activity. Lys33 was a key residue for maintaining dimer interaction when RTR residues were truncated but was not sufficient to keep efficient enzymatic reaction. The structural data can provide a potential target to develop novel therapeutic approaches to overcome multiresistance of the bacterium against antibiotics.

Abstract:The nptⅡ gene, encoding neomycin phosphotransferase Ⅱ, is one of the most commonly used selection marker in transgenic research. In this study, recombinant NPTⅡ protein was expressed in E. coli and monoclonal antibodies were generated. The inheritance, temp-spatial profiling, abundance and subcellular localization properties were investigated using established Western blot (WB) analysis. The results showed that NPTⅡ protein in 0.25% of a single rice grain (about 0.025mg) was detectable, the expression of NPTⅡ protein is consistent with dominant inheritance law, positive seeds and homozygous lines can be identified in transgenic T₁ generation, furthermore, the abundance of NPTⅡ protein can provide clues for the identification of homozygous individual in T₁ seedlings. Quantitative analyses shows that NPTⅡ protein accounts for about 0.08‰ of total protein in the leaves at seedling stage. The expression profile of NPTⅡ protein in transgenic rice shows that the abundance of NPTⅡ driven by CaMV-35S promoter in the leaves and roots at seedling and adult stage are higher than that at tillering and booting stage. NPTⅡ was detectable at different stages in rice root, stem, leaf, panicle, flower and seed, however, the abundance of NPTⅡ in tillers, node, panicle axis and anther tissues is lower than others. In addition, the NPTⅡ protein is mainly localized in the soluble portion of cytoplasm. Taken together, an applicable immunoblot method was established and the expression properties of NPTⅡ protein in transgenic rice were demonstrated.

Abstract:The importance of DNA methylation in neurodegenerative diseases has been increasingly recognized. We explored role of DNA methylation in the pathogenesis of Parkinson's disease in mouse model induced by MPTP. The global DNA methylation levels of substantia nigra region were measured by ELISA Kit. Expression of Dnmt1 and Dnmt3a were measured by Real-time PCR. Genome-wide profile was performed using methylated DNA immunoprecipitation microarray (MeDIP-Chip). Methylation status of differential methylated gene was validated by bisulfate sequencing and expression of differential methylated gene was determined by Real-time PCR. We have demonstrated that global methylation level was significantly decreased while expression levels of Dnmt1 was significantly increased in substantia nigra region of MPTP-induced mouse model compared to saline controls. Genome-wide DNA methylation analysis detected 48 sites, involving 44 genes, with significantly altered DNA methylation. The abnormal-methylated genes involved in the biological processes concerning signal transduction, molecular transport, transcription modulation, development, cell differentiation, regulation of apoptosis, oxidation reduction and protein catabolism. The methylation levels of promoter region of Uchl1 in substantia nigra region of MPTP-treated mice were significantly higher than that in the saline controls, with significant decreased expression of mRNA and protein. The methylation levels of promoter region of Arih2 in substantia nigra region of MPTP-treated mice were significantly decreased than that in the saline controls, with significant increased expression of mRNA and protein. These results suggested that DNA methylation were altered in substantia nigra region of MPTP-induced PD model. DNA methylation may play important role in the pathogenesis of PD induced by environmental factors such as MPTP.

Abstract:The initiation and progression of complex diseases have a close relationship with dysfunction of biological pathways in our body. Developing computational techniques to study the relationship between diseases and pathways through high-throughput data has essential biological significance. However, the traditional identification approaches of pathways which are significantly related to experiment conditions usually reduce pathways to gene sets. It is obvious that these methods do not consider the interactions between genes and the different roles that genes play in pathways, and they don't fully mine pathway information. Therefore we integrated protein-protein interaction information and gene weights into pathway analysis, and constructed a protein-pathway network which contains information in protein-protein interactions and pathways. We then scored pathways by random walk algorithm to optimize disease risk pathways. Finally, the statistically significant pathway can be identified through permutation method. We applied the network to a colorectal cancer dataset, and finally identified fifteen pathways which are significantly related to the development of this disease. Compared with other pathway identification methods (hypergeometric test and SPIA), our approach can effectively identify risk pathways related to complex diseases. In order to test the stability of our method in identifying risk pathways related to diseases, we used our method to identify risk pathways by using another colorectal cancer dataset. We found that the identified results can prove the stability of our method.