Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Neovascular Age-Related Macular Degeneration

Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Neovascular Age-Related Macular Degeneration Russell Simmers, Depts. of Physics and Chemistry, with Dr. Qingguo Xu, VCU School of Pharmacy Background: Neovascular age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly population in the industrialized world. The current treatment for neovascular AMD is anti-vascular endothelial growth factor (anti-VEGF) therapy; however, nearly 40-50% of patients do not fully respond to anti-VEGF therapy. Therefore, non-VEGF therapeutics are required for neovascular AMD treatment. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist and has demonstrated robust therapeutic effects on neovascular AMD in animal models; however, it must be delivered frequently via intravitreal injection due to quick clearance of the drug from the eye, and may induce injection associated side effects such as retinal detachment, ocular hemorrhage and endophthalmitis. Purpose: To develop and optimize fenofibrate-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Feno-NP) with high-drug loading and long-lasting drug release profile to effectively treat neovascular AMD for 6-months with one single intravitreal injection. Methods: Feno-NPs were prepared by emulsification method and were fully characterized in terms of particle size, surface charge, morphology and in vitro drug release profiles and the ocular pharmacokinetics studies were performed in rats following intravitreal injection. Efficacy on neovascular-AMD was determined by measuring vascular leakage, vascular permeability, and the numbers of subretinal neovascular (SRNV) and intraretinal neovascular (IRNV) lesions after intravitreal injection of Feno-NPs in a laser-induced choroid neovascularization (CNV) rat model.https://scholarscompass.vcu.edu/uresposters/1387/thumbnail.jp

Cold gas and a Milky Way-type 2175 {\AA} bump in a metal-rich and highly depleted absorption system

We report the detection of a strong Milky Way-type 2175 \AA$$ extinction bump at $z$ = 2.1166 in the quasar spectrum towards SDSS J121143.42+083349.7 from the Sloan Digital Sky Survey (SDSS) Data Release 10. We conduct follow up observations with the Echelle Spectrograph and Imager (ESI) onboard the Keck-II telescope and the Ultraviolet and Visual Echelle Spectrograph (UVES) on the VLT. This 2175 \AA$$ absorber is remarkable in that we simultaneously detect neutral carbon (C I), neutral chlorine (Cl I), and carbon monoxide (CO). It also qualifies as a damped Lyman alpha system. The J1211+0833 absorber is found to be metal-rich and has a dust depletion pattern resembling that of the Milky Way disk clouds. We use the column densities of the C I fine structure states and the C II/C I ratio (under the assumption of ionization equilibrium) to derive the temperature and volume density in the absorbing gas. A Cloudy photoionization model is constructed, which utilizes additional atoms/ions to constrain the physical conditions. The inferred physical conditions are consistent with a canonical cold (T $\sim$ 100 K) neutral medium with a high density ($n$(H I) $\sim$ 100 cm$^{-3}$) and a slightly higher pressure than the local interstellar medium. Given the simultaneous presence of C I, CO, and the 2175 \AA$$ bump, combined with the high metallicity, high dust depletion level and overall low ionization state of the gas, the absorber towards J1211+0833 supports the scenario that the presence of the bump requires an evolved stellar population.Comment: 18 pages, 17 figures, to be published in MNRA

Response Characteristics of Looseness-Rubbing Coupling Fault in Rotor-Sliding Bearing System

For the diagnosis of looseness-rubbing coupling fault of rotor-sliding bearing system caused by bolt looseness fault, the mechanical model and finite element model of dual-disc rotor system with looseness-rubbing coupling fault are established based on the nonlinear finite element method, nonlinear oil film force, looseness stiffness model, and Hertz contact theory. With the augmented Lagrange method, contact constraint conditions are dealt with to ensure that the rotary disk and casing contact with each other meeting boundary penetrating depth within the prescribed tolerance range. And then the dynamics characteristics of the health rotor system supported by sliding bearing are studied. Combined with experimental study and simulation analysis, it is found that the looseness-rubbing coupling fault is often characterized by rubbing fault, the lower part of the time-domain fluctuated shape is denser, while the upper part is relatively loose, and multiple nested half ellipse is shown in orbit diagram. Because of the loosing stiffness and rubbing force, the phenomenon of unstable oil film is depressed. The appearance of the first- and second-order oil film oscillation phenomenon is delayed. It could be used as a theoretical basis for diagnosing looseness-rubbing coupling fault of rotor-sliding bearing system

Associations between obesity, smoking behaviors, reproductive traits and spontaneous abortion: a univariable and multivariable Mendelian randomization study

BackgroundThe correlation between potential risk factors such as obesity (leg fat percentage (left), arm fat percentage (left), waist circumference, body fat percentage, trunk fat percentage), smoking behaviors (past tobacco smoking, smoking initiation, smoking/smokers in household, current tobacco smoking) and reproductive traits (age first had sexual intercourse (AFS), age at menarche (AAM), and age at first birth (AFB)) have been linked to the occurrence of spontaneous abortion (SA). However, the causal associations between these factors and SA remain unclear.MethodsWe conducted univariable and multivariable Mendelian randomization (MR) analyses to evaluate the associations of obesity, smoking behavior and reproductive traits with SA. To select appropriate genetic instruments, we considered those that had reached the genome-wide significance level (P < 5 × 10–8) in their corresponding genome-wide association studies (GWAS) involving a large number of individuals (ranging from 29,346 to 1,232,091). SA was obtained from the FinnGen consortium, which provided summary-level data for 15,073 SA cases and 135,962 non-cases.ResultsAssessed individually using MR, the odds ratios (ORs) of SA were 0.728 (P = 4.3608×10-8), 1.063 (P = 0.0321), 0.926 (P = 9.4205×10-4), 1.141 (P = 7.9882×10-3), 5.154 (P = 0.0420), 1.220 (P = 0.0350), 1.228 (P = 0.0117), 0.795 (P = 0.0056), 1.126 (P = 0.0318), for one standard deviation (SD) increase in AFS, AAM, AFB, smoking initiation, smoking/smokers in household, arm fat percentage (left), leg fat percentage (left), waist circumference and body fat percentage, 0.925 (P = 0.4158) and 1.075 (P = 0.1479) for one SD increase in past tobacco smoking, trunk fat percentage for one SD increase in SA. In multivariable MR (MVMR), only AFS (OR = 0.802; P = 0.0250), smoking initiation (OR = 1.472, P = 0.0258), waist circumference (OR = 0.813, P = 0.0220) and leg fat percentage (left) (OR = 4.446, P = 0.043) retained a robust effect.ConclusionSmoking behaviors, reproductive traits and obesity-related anthropometric indicators are potential causal factors for SA. Higher leg fat percentage; smoking initiation; and lower waist circumference and AFS may increase the risk of SA. Understanding the causal relationship for SA may provide more information for SA intervention and prevention strategies