Proliferative Activity and Neuroprotective Effect of Ligustrazene Derivative by Irritation of Vascular Endothelial Growth Factor Expression in Middle Cerebral Artery Occlusion Rats

Purpose: To investigate the proliferative activity and neuroprotective effect of a newly identified ligustrazine derivative (4-((3,5,6-trimethylpyrazine-2 yl)methoxyl)-3-methox-ybenzoic acid-3,5,6- trimethylpyrazin- 2-methyl ester, T VA) and the possible mechanism related to vascular endothelial growth factor (VEGF) in cerebral ischemic injury.Methods: The pharmacological activity of T-VA was evaluated using MTT ((3 (4,5-dimethylthiazolyl2- yl)-2,5-diphenyltetrazolium bromide)) assay, while cellular morphology was observed with hematoxylin and eosin (HE) staining. Chick chorioallantoic membrane (CAM) model, immuno-histochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of VEGF. Middle cerebral artery occlusion (MCAO) model was used to investigate both VEGF expression and the survival rate after treatment with T-VA.Results: T-VA promoted neuron activity, and the doses of 15 and 30 μM showed more significant effect (p < 0.05). The viability of PC12 cells increased significantly in T-VA (30 and 60 μM) groups (p < 0.05) and increased in a dose dependent manner. Immunohistochemical analysis showed stimulated VEGF expression, and CAM model results showed that T-VA (20 mg/egg) significantly promoted microangiogenesis (p < 0.01). Moreover, in MCAO model, the survival rate of T-VA (60 mg/kg) group reached 86.7 % while for the ischemia group it was 60.0 %. In addition, ELISA results showed that T-VA promoted the expression of VEGF (p < 0.05).Conclusion: These findings indicate that T-VA helps to prevent ischemic injury by increasing VEGF expression.Keywords: Ligustrazine, Neuron, PC12 cell, Chick Chorioallantoic Membrane, Middle Cerebral Artery Occlusion, Vascular Endothelial Growth Facto

Case Report: Chronic hepatitis E virus Infection in an individual without evidence for immune deficiency

Chronic hepatitis E virus (HEV) infection occurs mainly in immunosuppressed populations. We describe an investigation of chronic HEV infection of genotype 3a in an individual without evidence for immune deficiency who presented hepatitis with significant HEV viremia and viral shedding. We monitored HEV RNA in plasma and stools, and assessed anti-HEV specific immune responses. The patient was without apparent immunodeficiency based on quantified results of white blood cell, lymphocyte, neutrophilic granulocyte, CD3+ T cell, CD4+ T cell, and CD8+ T cell counts and CD4/CD8 ratio, as well as total serum IgG, IgM, and IgA, which were in the normal range. Despite HEV specific cellular response and strong humoral immunity being observed, viral shedding persisted up to 109 IU/mL. After treatment with ribavirin combined with interferon, the indicators of liver function in the patient returned to normal, accompanied by complete suppression and clearance of HEV. These results indicate that HEV chronicity can also occur in individuals without evidence of immunodeficiency

A novel stationary wavelet denoising algorithm for array-based dna copy number data

Abstract: High-throughput array-based assays have recently been developed to detect DNA copy number (DCN) aberrations. The DCN data from these arrays is characterized by high level of noise and unequal spacing of the probes on the genome. However, previously proposed denoising methods for DCN data did not consider the physical distances of the probes and assumed uniform spacing. It can be shown that denoising methods assuming uniform spacing for DCN data can potentially give incorrect results. To address this issue, we developed a novel stationary wavelet denoising scheme based on interpolation for DCN data. Empirical results on synthetic data showed that our method outperformed the best previously proposed wavelet denoising method by 4.6 % – 12.7 % as measured in the root mean squared error. Experiments on a real data set also confirmed the applicability of our method to real DCN data

Int. J. Pharm.

Oral delivery of antigens is patient-friendly and efficient way of treating intestinal infections. However, the efficacy of oral vaccines is limited by degradation in the gastrointestinal (GI) tract and poor absorption by enterocytes and antigen-presenting cells (APC). Here we report ulex europaeus agglutinin-1 (UEA-1) conjugated poly (D,L-lactide-co-glycolide) (PLGA)-lipid nanoparticles (NP) containing a Toll-like receptor (TLR)-agonist monophosphoryl lipid A (MPL) as an oral vaccine delivery system. The uniform-sized PLGA-lipid NPs (simplified as lipid NPs) were produced by the premix membrane emulsification method. They can protect the entrapped model antigen ovalbumin (OVA) from exposure to the GI tract and release the OVA in a controlled manner. With UEA-1 and MPL modification, the UEA-MPL/lipid NPs can be effectively transported by M-cells and captured by mucosal dendritic cells (DCs). After in vivo vaccination, the OVA-UEA-MPL/lipid NPs stimulated the most effective mucosal IgA and serum IgG antibodies during the oral formulations. These results suggest that this MPL containing M-cell targeted lipid NP can potentially be used as a universally robust oral vaccine delivery system. (C) 2014 Elsevier B.V. All rights reserved.Oral delivery of antigens is patient-friendly and efficient way of treating intestinal infections. However, the efficacy of oral vaccines is limited by degradation in the gastrointestinal (GI) tract and poor absorption by enterocytes and antigen-presenting cells (APC). Here we report ulex europaeus agglutinin-1 (UEA-1) conjugated poly (D,L-lactide-co-glycolide) (PLGA)-lipid nanoparticles (NP) containing a Toll-like receptor (TLR)-agonist monophosphoryl lipid A (MPL) as an oral vaccine delivery system. The uniform-sized PLGA-lipid NPs (simplified as lipid NPs) were produced by the premix membrane emulsification method. They can protect the entrapped model antigen ovalbumin (OVA) from exposure to the GI tract and release the OVA in a controlled manner. With UEA-1 and MPL modification, the UEA-MPL/lipid NPs can be effectively transported by M-cells and captured by mucosal dendritic cells (DCs). After in vivo vaccination, the OVA-UEA-MPL/lipid NPs stimulated the most effective mucosal IgA and serum IgG antibodies during the oral formulations. These results suggest that this MPL containing M-cell targeted lipid NP can potentially be used as a universally robust oral vaccine delivery system. (C) 2014 Elsevier B.V. All rights reserved

Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin

In this study, a polymeric lipid nanoparticle (NP) (simplified as Lipid NP) was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide) (PLGA) core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA) was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC) and entrapment efficiency (EE) for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI) environment for a long time. In addition, a human microfold cell (M-cell) transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses

ST-PBFT: An Optimized PBFT Consensus Algorithm for Intellectual Property Transaction Scenarios

For the current Intellectual Property (IP) transaction scenario, consensus nodes need to simultaneously consensus transactions of the same transaction type, resulting in low consensus efficiency, accuracy, and reliability, which seriously hinders the development of intellectual property. Based on the consortium chain, this paper proposes a secure and efficient blockchain-distributed consensus algorithm, ST-PBFT (Shard Transaction Practical Byzantine Fault Tolerance), applied to the IP transaction scenario. The main contributions of ST-PBFT include the following: first, a grouping method based on the principle of consistent hashing is proposed to group consensus nodes, and nodes group consensus, which reduces the complexity of communication. Second, the transaction consensus group can process IP transactions in parallel, which improves the throughput of the algorithm. Third, a node reputation evaluation model is proposed, which can prevent byzantine nodes from being repeatedly elected as primary nodes. The experimental results show that ST-PBFT can significantly improve the consensus efficiency and reliability and reduce consensus latency

Colloid Surf. B-Biointerfaces

The main challenge in the oral delivery of protein drugs is to enhance their oral bioavailability. Herein, we report the uniform-sized liposphere prepared by premix membrane emulsification combined with W-1/O/W-2 double-emulsion method as a potential oral carrier for proteins. The protein-loaded liposphere was composed of a hydrophobic poly (D, L-lactide-co-glycolide) (PLGA) core and the lipid molecules self-assembled at the interface of W-1/O and O/W-2. During the preparation, the protein structure was effectively maintained. Compared with PLGA microsphere, the liposphere achieved a higher loading capacity (LC, 20.18%), entrapment efficiency (EE, 90.82%) and a lower initial burst (24.73%). Importantly, the lipospheres also showed high transcytotic efficiency with human microfold cell (M cell) model, leading to a potential enhancement of intestinal absorption. This result, together with the above studies supported that the PLGA-lipid liposphere could be a promising platform for enhancing the proteins oral bioavailability. (C) 2014 Elsevier B.V. All rights reserved.The main challenge in the oral delivery of protein drugs is to enhance their oral bioavailability. Herein, we report the uniform-sized liposphere prepared by premix membrane emulsification combined with W-1/O/W-2 double-emulsion method as a potential oral carrier for proteins. The protein-loaded liposphere was composed of a hydrophobic poly (D, L-lactide-co-glycolide) (PLGA) core and the lipid molecules self-assembled at the interface of W-1/O and O/W-2. During the preparation, the protein structure was effectively maintained. Compared with PLGA microsphere, the liposphere achieved a higher loading capacity (LC, 20.18%), entrapment efficiency (EE, 90.82%) and a lower initial burst (24.73%). Importantly, the lipospheres also showed high transcytotic efficiency with human microfold cell (M cell) model, leading to a potential enhancement of intestinal absorption. This result, together with the above studies supported that the PLGA-lipid liposphere could be a promising platform for enhancing the proteins oral bioavailability. (C) 2014 Elsevier B.V. All rights reserved

Phase Optimization for Massive IRS-aided Two-way Relay Network

In this paper, with the help of an intelligent reflecting surface (IRS), the source (S) and destination (D) exchange information through the two-way decode-and-forward relay (TW-DFR). We mainly focus on the phase optimization of IRS to improve the system rate performance. Firstly, a maximizing receive power sum (Max-RPS) method is proposed via eigenvalue decomposition (EVD) with an appreciable rate enhancement, which is called Max-RPS-EVD. To further achieve a higher rate, a method of maximizing minimum rate (Max-Min-R) is proposed with high complexity. To reduce its complexity, a low-complexity method of maximizing the sum rate (Max-SR) via general power iterative (GPI) is proposed, which is called Max-SR-GPI. Simulation results show that the proposed three methods outperform the case of random phase method, especially the proposed Max-SR-GPI method is the best one achieving at least 20\% rate gain over random phase. Additionally, it is also proved the optimal rate can be achieved when TW-DFR and IRS are located in the middle of S and D.Comment: 9 pages,10 figure