NF-κB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK pathway

Abstract4-Hydroxyhexenal (HHE) is known to affect redox balance during aging, included are vascular dysfunctions. To better understand vascular abnormality through the molecular alterations resulting from HHE accumulation in aging processes, we set out to determine whether up-regulation of mitogen-activated protein kinase (MAPK) by HHE is mediated through nuclear factor kappa B (NF-κB) activation in endothelial cells. HHE induced NF-κB activation by inhibitor of κB (IκB) phosphorylation via the IκB kinase (IKK)/NF-κB inducing kinase (NIK) pathway. HHE increased the activity of p38 MAPK and extracellular signal regulated kinase (ERK), but not c-jun NH2-terminal kinase, indicating that p38 MAPK and ERK are closely involved in HHE-induced NF-κB transactivation. Pretreatment with ERK inhibitor PD98059, and p38 MAPK inhibitor SB203580, attenuated the induction of p65 translocation, IκB phosphorylation, and NF-κB luciferase activity. These findings strongly suggest that HHE induces NF-κB activation through IKK/NIK pathway and/or p38 MAPK and ERK activation associated with oxidative stress in endothelial cells

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

The complete chloroplast genome of Cirsium japonicum (Asterales: Asteraceae)

Cirsium japonicum (C. japonicum) is an important oriental herb belonging to the family Asteraceae. The C. japonicum complete chloroplast genome is composed of 152,606 bp, which form a large single-copy region (LSC, 83,492 bp), a small single-copy region (SSC, 18,772 bp), and 2 inverted repeats (IRs, 25,196 bp). There are 114 genes annotated, including 80 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. Our phylogenetic analysis suggests that C. japonicum is closely related to the Cirsium genus of the Asteraceae family, and that C. japonicum (subfamily: Carduoideae) is separate from the Asteroideae subfamily

Theoretical study on the interaction between candidate drugs and Coronavirus main protease (3CLPro) for inhibiting replication of SARS-CoV-2

We theoretically investigated the interactions of drug molecules with 3C-like protease (3CLPro), to inhibit the replication of SARS-CoV-2 using molecular dynamics (MD) simulation. Lopinavir, Ritonavir, CG376 and dipeptidyl series were used at different temperatures and concentrations. The adsorption behavior of drug candidates was compared by analyzing the root mean square fluctuation (RMSF) of 3CLPro, minimum distances and interaction energies between 3CLPro and drug and radial distribution function(RDF). The drugs were mainly adsorbed on the 3CLpro by the polar interactions. In specifically, dipeptidyl 7a was effective in inhibiting 3CLPro since it shows high binding energy, high number of attached active sites 3CLPro and compared to those of dipeptidyl 6c. In specifically, alkyl groups within drugs mainly sticked to the active sites of 3CLPro. As higher concentration, the interactions between drugs and the protein were increased, which was shown by larger adsorption area of drugs on the protein, and however, average of interaction energy is lower. Meanwhile, the number of adsorbed drugs was similar in different temperature of the drug

The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory

Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction. © The Author(s) 201811Nsci

Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-<i>g</i>-Chitosan Copolymer

Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties

Multiple roles of palladium-coated magnetic anisotropic particles as catalysts, catalyst supports, and micro-stirrers

We report the external field-guided shape transformation of magnetite-polymer composite particles that play multiple roles in heterogeneous chemical reactions, such as catalysts, catalyst supports, and micro-stirrers. A microfluidic method was used to generate monodispersed emulsion droplets composed of polystyrene, magnetite nanoparticles (MNPs), and chloroform. While the solvent in the droplets was dried in the presence of an external magnetic field, the emulsion droplets were deformed or elongated along the field direction, consequently leading to magnetically responsive particles with anisotropic shape after complete removal of the solvent. Coarse-grained molecular dynamic simulations demonstrated that the shape deformation was due to destabilization of the MNPs upon solvent drying and migration of the aggregated MNPs in the polymer matrix along the external field. The particle shape could be readily tunable by modulating the field strength and direction as well as the concentrations of the MNPs and polymer. We further revealed that these magnetic anisotropic particles coated with palladium nanoparticles could be used as catalysts, catalyst supports, micro-stirrers when the particles were dispersed in a small confined volume of a catalytic precursor solution

One-step production of highly anisotropic particles via a microfluidic method

We introduce a promising protocol that can be used to fabricate polymer particles with a high degree of shape anisotropy; this method can be utilized with a variety of microfluidic generation methods. Low-density microparticles and high-density nanoparticles vertically migrated in a polymer solution confined in emulsion droplets that were produced via a microfluidic method. As the solvent evaporated in individual droplets at ambient conditions, the low-density microparticles migrated upward because their density was lower than that of the polymer solution. The high-density nanoparticles that were initially well-dispersed in the droplet phase became destabilized upon solvent removal, leading to the formation of aggregates and sedimentation in a downward direction. The migration of the particle components during solvent evaporation induced shape deformation/modification of the emulsion droplets; consequently, polymer particles with highly anisotropic shapes were created after drying

PAR2 Deficiency Induces Mitochondrial ROS Generation and Dysfunctions, Leading to the Inhibition of Adipocyte Differentiation

Protease-activated receptor 2 (PAR2) is a member of G-protein-coupled receptors and affects ligand-modulated calcium signaling. Although PAR2 signaling promotes obesity and adipose tissue inflammation in high fat- (HF-) fed conditions, its role in adipocyte differentiation under nonobesogenic conditions needs to be elucidated. Here, we used several tissues and primary-cultured adipocytes of mice lacking PAR2 to study its role in the development of adipose tissues. C57BL/6J mice with PAR2 deficiency exhibited a mild lipodystrophy-like phenotype in a chow diet-fed condition. When adipocyte differentiation was examined using primary-cultured preadipocytes, PAR2 deficiency led to a notable decrease in adipocyte differentiation and related protein expression, and PAR2 agonist treatment elevated adipocyte differentiation. Regarding the mechanism, PAR2-deficient preadipocytes exhibited impaired mitochondrial energy consumption. Further studies indicated that calcium-related signaling pathways for mitochondrial biogenesis are disrupted in the adipose tissues of PAR2-deficient mice and PAR2-deficient preadipocytes. Also, a PAR2 antagonist elevated mitochondrial reactive oxygen species and reduced the MitoTracker fluorescent signal in preadipocytes. Our studies revealed that PAR2 is important for the development of adipose tissue under basal conditions through the regulation of mitochondrial biogenesis and adipocyte differentiation