Abstract:Influenza A virus causes annual epidemics, and occasional pandemics that bring a significant global health threat. Influenza virus, which belongs to the Orthomyxoviridae family, is an enveloped virus that contains a segmented and negative-sense RNA genome. The assembly and budding of progeny influenza is a complicated and multi-step process involving many viral factors. Influenza budding occurs in lipid raft domains of cells membrane. Firstly, two viral glycoproteins HA and NA, concentrate in lipid rafts to initiate the budding process by causing membrane enlargement and curvature. Secondly Matrix protein 1 (M1), which forms the inner virion matrix, is then recruited to the budding site followed by the incorporation of viral VPNPs and M2 proteins. In the later stages of budding, M2 is concentrated to the bottom of the budding virion at the lipid rafts boundary, resulting in viral scission and virion release.

Abstract:Asialoglycoprotein receptor (ASGPR) was specifically expressed by hepatocytes, which could recognize and bind asialoglycoprotein, galactose (Gal), galactosamine, N-acetylgalactosamine (GalNAc), etc. with high affinity. In a receptor-mediated-endocytosis (RME) manner, various molecules could be delivered into hepatocytes effectively. In this review, we firstly introduced the discovery, structure, function, expression pattern and endocytosis properties of ASGPR. Then the influence factors of ligand/receptor interaction and RME, including ligand species, valence, orientation and particle size, were analyzed. In addition, studies on ASGPR-mediated drug delivery in the past decades were reviewed. More importantly, progress in GalNAc-conjugation or -modification technologies employed in liver-targeted transportation of siRNA, antisense and antagomir were summarized.

Abstract:Osteogenesis imperfecta (OI) is a group of rare genetic connective tissue diseases with clinical heterogeneity and genetic heterogeneity. Till now, fifteen subtypes of OI has been identified. Autosomal dominant OI is the primary inheritance pattern, and it is caused by mutations in the COL1A1 or COL1A2 genes that encode the proa1 and proa2. Recessively inherited forms of OI are rare and are caused by mutations in many different genes, which related with post-transcriptional modification, defects of collagen's chaperons and C-propeptide cleavage enzyme, osteoblast/osteocyte differentiation and transcript factor, Ca²⁺ channel as well as Wnt signaling molecules. The pathogenic genes and mechanisms to dominant and recessive OI are useful for gene detection and individual therapy of OI patients.

Abstract:Implied motion is defined as extraction of motion information from a stationary photo. With low-level and high-level stimuli, researchers usually employ four paradigms (i.e., freeze-frame, passively viewing, motion aftereffect, and fMRI adaption) to investigate implied motion. The role of attention and awareness in implied motion and the memory representation of implied motion are key issues in previous studies. Researchers also focus on the various activated brain regions engaged in implied motion, including medial temporal cortical areas (MT/MST), superior temporal sulcus, and mirrorneuron system. Future studies are needed to further explore the cognitive and neural mechanisms of implied motion in order to clarify whether motion and form processing in human visual system, especially the neural network for motion from form, are dissociated or integrated.

Abstract:Alzheimer's disease(AD) is the most common neurodegenerative diseases characterized by the accumulation of two hallmark pathologies, extraneuronal senile plaques and intraneuronal neurofibrillary tangles. Although the exact mechanisms that trigger the pathological alterations of AD are still not clear, most studies have suggested a variety of pathological changes such as inflammation, oxidative stress, mitochondrial dysfunction, apoptosis and synaptic dysfunction, etc. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is activated by oxidative stress and regulates the expression of a variety of antioxidant enzymes and proteins that exert cytoprotective effects against oxidative stress. Numerous studies have addressed the role of Nrf2 against oxidative stress. Further, recent findings concerning that Nrf2 not only regulates antioxidant proteins but also regulates the genes associated with anti-inflammatory, anti-apoptotic and nerve growth factor signaling in AD. In addition, activation of the Nrf2 pathway may have the effect of anti-amyloidogenic and reduces the levels of phosphorylated tau. Recently all new anti-AD drugs focused on a single target have failed, so researchers put forward that activation of Nrf2 may be a good treatment for AD through simultaneous modulation of numerous pathways involved in AD pathogenesis. Here in this review we summarize the research status of Nrf2 in AD.

Abstract:Almost all biological processes are involved in the modulation of mechanical force whose functions are physically involved with cytoskeleton. This unique form of mechanical force is called structural mechanics and it is regulated realtime by a variety of factors, such as exogenous force, motor proteins, osmotic pressure, mechanosensitive ion channels (MSCs), intracellular mechanosensors and actin assembling. FRET-based force sensors which can be incorporated into structural proteins and turn structural force into optical signal can provide a realtime measurement of force in live cells. With the advent of the space age, structural dynamics will play a more and more important role in life and medical research.

Abstract:Exposure of pregnant females to strong prenatal stress generally induces psychotic-like behavioral impairments in their offspring. In contrast to strong stress exposure, mild prenatal stress exposure (MPSE) has been reported to increase the vulnerability of the nervous system to adverse environmental stimuli. However, the impacts of MPSE on treatment with antipsychotic medication have not been well investigated. In addition, although commonly utilized in animal experiments, the potential influences of injections per se on animal behavior have not been evaluated. Here, we investigated how MPSE, postnatal injections and olanzapine (OLZ) treatment might interact to affect the behavior of rats. Pregnant female rats were exposed to mild stress or left undisturbed during the last week of gestation. Their offspring were divided into three sub-groups and subjected to injections with saline or OLZ (2 mg/kg) on postnatal days (PDs) 7, 9 and 11 or were left undisturbed without injection. Social and olfactory discrimination tests were performed during adolescent (PD 35) and adult (PD 60) periods. Total exploratory time and the degree of preference in the discrimination tests were measured. We found that postnatal injections changed the degree of preference in adolescent prenatally stressed rats but had no effect on the degree of preference in the non-stressed rats. OLZ treatment increased the social exploratory time in the non-stressed rats during the adolescent and adult periods. However, these enhancing effects were diminished in the prenatally stressed rats. Our results indicate that MPSE could contribute to the behavioral changes induced by adverse stimuli such as postnatal injections and could reduce the treatment effects of antipsychotic medication.

Abstract:Hemagglutinin(HA)is a type Ⅰ transmembrane glycoprotein which is located in the surface of the influenza virus envelope. It plays a pivotal role in binding with sialyloligosaccharides receptor on host cell surface and mediated viral entry into cells. It is also the important target of neutralizing antibodies and vaccine development. The glycosylation of HA is closely associated with viral virulence, host range and other infections. In addition, glycosylation and pattern alterations also affect the structural roles as well as diverse functional roles of HA in many specific biological process. However, little is known about the precise glycan structures on the surface of HA. In this study, we prepared a specific SAα2-3Gal Magnetic Particle Conjugates, which was used to purify HA from avian influenza A (H7N2) virus. The isolated HA was identified by SDS-PAGE and MALDI-TOF-MS. Then, the glycan profile of HA was analyzed by the lectin microarrays and mass spectrometry. The results showed that the glycan structures such as fucose, galactose, N-acetylgalactosamine, mannose, and N-acetylglucosamine were expressed on the surface of HA and 16 glycans with the precise structure were acquired. These glycans may be associated with the biological functions of HA, and helps to reveal the glycan mechanism of avian influenza virus how to effect the host specificity, virulence and infectivity of the influenza virus, as well as design the vaccine based on glycan structures on the surface of HA.

Abstract:The important role of phospholipids in many processes including cell cycle regulation, inflammation and tumorigenesis is increasingly becoming the focus of research. Previously we found that cytosolic phospholipase A2 (cPLA2) is over-expressed in breast cancer cells. Here, we assessed the profiles of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) that were mediated by cPLA2 in breast cancer cells. MCF-7 and LM-MCF-7 (with high metastatic potential) cell lines were used as models and the profiles of phospholipids were analyzed by HPLC/ESI/MSⁿ. Our results showed that the levels of 10 species of LysoPCs were higher in LM-MCF-7 cells than that in MCF-7 cells. Meanwhile, six species of PCs that may produce arachidonic acid (AA) and associated LysoPCs were lower in LM-MCF-7 cells than that in MCF-7 cells. Furthermore, we identified that 4 out of 6 species of PCs were responsible for the generation of AA mediated by cPLA2 in LM-MCF-7 cells. The increased ratio of LysoPCs to PCs corresponds to the activation level of cPLA2. Thus, we conclude that 4 identified species of PCs and 4 corresponding species of LysoPCs mediated by cPLA2, as well as the up-regulation and activation of cPLA2, may involve in the metastasis of breast cancer cells.

Abstract:Talin, as the activator of integrin and the adaptor between the cytoskeleton and integrin, plays a key role in a series of processes such as cell adhesion and migration．The activation of integrin involves F3 subdomain of Talin-FERM domain binding the cytoplasmic tail of integrin β-subunit．Talin has two states: auto-inhibited and activated．We previously reported the auto-inhibition complex structure of Talin F2F3/R9, in which the integrin binding site F3 interacts with R9(1654～1822 a.a.) of Talin-ROD, such that integrin cannot be activated. However, besides F3 and R9, it remains unclear what structural or functional roles the other domains of the 270 ku Talin play in the regulation of its activation．Here we solved the crystal structures of Talin R9-R10 (1654～1973 a.a.) and R10-R11 (1815～2140 a.a.), respectively．R9, R10 and R11 are all 5-helix bundles．R9 and R10 is joined together by a long α-helix instead of a flexible loop, and the two bundles are located at the opposite sides of the long helix with an angle of about 150°．The linker between R10 and R11 is stabilized by neighboring hydrogen bonds, forming an angle of about 120° between the two bundles．These angles observed in our crystal structures are consistent with the previously reported SAXS and EM results．After superimposition of R9-10, R10-11 with previously reported structures of R7-8 and R11-12, a model of R7-12 was acquired, which adopts an elongated linear conformation, except that R8 protrudes from the ROD．According to this model, R10-12 does not intrude the interaction between F3 and R9, whereas R8 not only masks the F3 binding site of R9, but also might electrostatically hinders F2F3 approaching via its unique positively charged surface．This hypothesis was further verified by the results of size exclusion chromatography．Our work provides a new structural basis for studying the mechanism of Talin auto-inhibition.

Abstract:Biofilm (bacterial biofilm, BF) are associated with most bacterial infections, which can help pathogens against adverse environment, such as antibiotic and phages. In order to exploid the mechanism involved with BF formation and anti-phage, six Salmonella paratyphi A (S. paratyphi A) mutants resistant to phage were analyzed in this study. Phages were dropped on bacteria line on LB plate containing Rif⁺(200 mg/L)to confirm phage resistance. Six mutants were cultured in 96 well plate with three replications to monitor biofilm formation and morphology. Site-directed mutagenesis and complementation test were used to confirm whether phage resistance was caused by gene mutant. Results of this study showed that all six mutants were resistant to phage, because those could growth with dropped 2.4×10⁹ phages and wild bacteria could not with dropped 1.2×10⁶ phages. Among six mutants, BF formation of mutant of σ-54-dependent translation regulator was significantly enhanced contrast with wild bacteria (P < 0.05, 1.1±0.2 vs 0.5±0.1). Bacteria aggregated to large irregular mass. Site-directed mutation of σ-54-dependent translation regulator with homologous recombination led to be resistant to phages. This resistance could be recovered by supplemented with plasmid expressed σ-54-dependent translation regulator. All those showed that σ-54-dependent translation of the regulator was associated with anti-phage and BF formation.