Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization

Purpose: To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Methods: Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. Results: In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01 +/- 4.49/mm(2) versus 48.68 +/- 9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68 +/- 9.30/mm(2) versus 74.38 +/- 9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01 +/- 4.49/mm(2) versus 74.38 +/- 9.23/mm(2), p<0.001). Conclusions: Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000281341400003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyOphthalmologySCI(E)PubMed7ARTICLE187-891743-17531

Rejuvenation Effect of Aged SBS-Modified Asphalt Utilizing Molecule Analysis

The Performance of Styrene-Butadiene-Styrene Modified Asphalt (SBSMA) is Significantly Impacted by its Aging and Regeneration. in This Research, the Molecular Dynamics Simulation Was Utilized to Investigate the Rejuvenation Effect of Active Reagents on Aged SBS Modified Asphalt through the Following Tasks: 1) Verifying the Accuracy of the Asphalt Model by Density and Solubility Parameters; 2) Assessing the Changes in the Rejuvenated Asphalt Model\u27s Energetic Parameters and Volume Parameters, 3) Studying the Interaction Energy between SBS Molecules and Asphalt Molecule Models, and 4) Evaluating the Relative Concentration, Interfacial Interaction Energy, and Diffusion Effect of the Asphalt-Asphalt Models. the Results Indicated that the Restored Broken SBS Molecule Substantially Impacted the Functionality of the Rejuvenated Asphalt Binder. for Methylene-Bis(4-Cyclohexylisocyanate) (HMDI) and 1,6-Hexanediol Diglycidyl Ether (HDE) Rejuvenated Asphalts, the Non-Bond Energy Decreased Gradually with the Repair of Broken SBS Molecular Structures. the Free Volume Fraction of Rejuvenated Binders Was Lower Than that of SBSMA, indicating that the Compactness and Packing Degree of the Rejuvenated Asphalt Were Increased. the Interaction Energy between SBS and Asphalt Molecules in Rejuvenated Asphalt Increased Because of the Enhanced Van Der Waals Interaction between the Reconstructed SBS Molecule and Rejuvenated Binders. the Free HDE Molecular Chain Reduced the Interaction Energy between SBS and Asphalt Molecules. for the Asphalt-Asphalt Models, the Diffusion Coefficient of the SBSMA-Rejuvenated Asphalt Model Was Lower Than that of the SBSMA-SBSMA Model. the HDE Rejuvenated Asphalt Showed Better Diffusion Behavior Than SBSMA, and SBS Molecules Repaired by HDE Had Excellent Fluidity. the Interfacial Interaction Energy of the SBSMA-Rejuvenated Asphalt Model Was Higher Than that of the SBSMA-SBSMA Model. with the Repair of the Broken SBS Molecular Chain, the Interfacial Interaction Energy between HMDI Rejuvenated Asphalt and SBSMA Increased Gradually. in Contrast, the Interfacial Interaction Energy between HDE Rejuvenated Asphalt and SBSMA Decreased Gradually. the Fully Restored SBS Molecular Structure Had Stable Thermodynamic Properties and Could Accelerate the Diffusion Effect of Rejuvenated Asphalt

Evolution Of SBS-Modified Asphalt Performance Under Aging And Rejuvenation Cycle Conditions

Improving the poor long-term service performance of rejuvenated SBS-modified asphalt (REF-LT) is highly challenging. In this study, a blend of aged and virgin binders was used to rejuvenate REF-LT and the evolution of the asphalt performance was observed during regeneration and reaging processes. An SBS-modified asphalt (SBM) and base asphalt (BA) were mixed with REF-LT in specified ratios to prepare SBM- and BA-rejuvenated asphalts. The rejuvenated asphalts were subjected to short- and long-term aging. The high/low-temperature rheological properties, fatigue resistance, rejuvenation mechanism, and changes in the functional groups of the rejuvenated and reaged asphalts were characterized using a dynamic shear rheometer (DSR) and Fourier transform infrared spectroscopy (FTIR). The antiaging performance of the rejuvenated asphalt was evaluated. Temperature sweep results showed that both SBM and BA mitigated hardening in REF-LT. BA had a stronger softening effect on REF-LT than SBM. However, the BA-rejuvenated asphalt was more temperature sensitive than the SBM-rejuvenated asphalt. The BA-rejuvenated asphalt had poor resistance to reaging, whereas the SBM-rejuvenated asphalt demonstrated outstanding resistance to long-term aging. The Glover–Rowe (G-R) parameters indicated that after short-term aging, the rejuvenated asphalts remained in the no cracking zone, demonstrating outstanding resistance to thermal cracking. A total of 20 h of long-term aging of the rejuvenated asphalts decreased the crossover frequency and increased the rheological index, suggesting an increased risk of cracking. Relaxation tests showed that the BA-rejuvenated asphalt had a lower peak stress than that of the SBM-rejuvenated asphalt; however, the durability of the BA-rejuvenated asphalt was compromised because of the peak stress rapidly increased after reaging. Although the BA-rejuvenated asphalt exhibited good short-term crack resistance, its poor durability resulted in inferior thermal crack resistance to that of the SBM-rejuvenated asphalt after long-term aging. Linear amplitude sweep (LAS) tests indicated that the SBM-rejuvenated asphalt had a lower damage rate than the BA-rejuvenated asphalt, suggesting that the polymer network structure provided excellent damage resistance. The fatigue life of the BA-rejuvenated asphalt decreased considerably after reaging, indicating insufficient long-term fatigue resistance. The FTIR results indicated that the REF-LT rejuvenation process involved physical blending and the SBM-rejuvenated asphalt exhibited superior antiaging capability to the BA-rejuvenated asphalt. Increasing the BA content did not improve the long-term antiaging performance of the BA-rejuvenated asphalt. The higher antiaging performance of the SBM-rejuvenated asphalt resulted from the polymer network structure

Study on Acoustic Emission In-situ Stress Measurement Techniques Based on Plane Stress Condition

AbstractIn-situ stress is the key parameter for underground and slope rock engineering design optimization. Hydraulic fracturing method and trepanning stress relieving method are the two main in-situ stress measurement methods for the present, but both of the two methods have some disadvantages such as strict operating conditions, complicated operations, high cost, etc. which have not been overcome till now. With a case of high-steep open pit slope, the paper begins with hydraulic fracturing method to measure the in-situ stress and then, on this basis, based on plane stress condition, the paper adopts acoustic emission method to measure the horizontal maximum principle stress and its direction. It indicates that the test results of acoustic emission are consistent with that of hydraulic fracturing method

Changes of predominant species/biovars and sequence types of Brucellaisolates, Inner Mongolia, China

BACKGROUND: Human brucellosis incidence in China was divided into 3 stages, high incidence (1950-1960s), decline (1970-1980s) and re-emergence (1990-2000s). Human brucellosis has been reported in all the 32 provinces, of which Inner Mongolia has the highest prevalence, accounting for over 40% of the cases in China. To investigate the etiology alteration of human brucellosis in Inner Mongolia, the species, biovars and genotypes of 60 Brucella isolates from this province were analyzed. METHODS: Species and biovars of the Brucella strains isolated from outbreaks were determined based on classical identification procedures. Strains were genotyped by multi locus sequence typing (MLST). Sequences of 9 housekeeping genes were obtained and sequence types were defined. The distribution of species, biovars and sequence types (STs) among the three incidence stages were analyzed and compared. RESULTS: The three stages of high incidence, decline and re-emergence were predominated by B. melitensis biovar 2 and 3, B. abortus biovar 3, and B. melitensis biovar 1, respectively, implying changes in the predominant biovars. Genotyping by MLST revealed a total of 14 STs. Nine STs (from ST28 to ST36), accounting for 64.3% of all the STs, were newly defined and different from those observed in other countries. Different STs were distributed among the three stages. ST8 was the most common ST in 1950-1960s and 1990-2000s, while ST2 was the most common in 1970-1980s. CONCLUSIONS: The prevalence of biovars and sequence types of Brucella strains from Inner Mongolia has changed over time in the three stages. Compared with those from other countries, new sequence types of Brucella strains exist in China