Our study was aimed at assessing the retinal binding of a new synthetic Brilliant Blue G (BBG) derivative (pure benzyl-Brilliant Blue G; PBB) ophthalmic formulation, to improve vitreoretinal surgery procedure. Protein affinity of the new molecule was evaluated in vitro (cell-free assay) and in silico. Furthermore, an ex vivo model of vitreoretinal surgery was developed by using porcine eyes to assess the pharmacological profile of PBB, compared to commercial formulations based on BBG and methyl-BBG (Me-BBG). PBB showed a higher affinity for proteins (p less then 0.05), compared to BBG and Me-BBG. In vitro and in silico studies demonstrated that the high selectivity of PBB could be related to high lipophilicity and binding affinity to fibronectin, the main component of the retinal internal limiting membrane (ILM). The PBB staining capabilities were evaluated in porcine eyes in comparison with BBG and Me-BBG. Forty microliters of each formulation were slowly placed over the retinal surface and removed after 30 s. After that, ILM peeling was carried out, and the retina collected. BBG, Me-BBG, and PBB quantification in ILM and retina tissues was carried out by HPLC analysis. PBB levels in the ILM were significantly (p less then 0.05) higher compared to BBG and Me-BBG formulations. On the contrary, PBB showed a much lower (p less then 0.05) distribution in retina (52 ng/mg tissue) compared to BBG and Me-BBG, in particular PBB levels were significantly (p less then 0.05) lower. Therefore, the new synthetic Brilliant Blue derivative (PBB) showed a great ILM selectivity in comparison to underneath retinal layers. In conclusion, these findings had high translational impact with a tangible improving in ex vivo model of retinal surgery, suggesting a future use during surgical practice.Background and objectives Lower vitamin status has been linked to cognitive deficits, pending mechanistic elucidation. Serum 25-hydroxyvitamin D [25(OH)D], folate and cobalamin were explored against brain volumes and white matter integrity (WMI). Methods Three prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were used [Baltimore, City, MD, 2004-2015, N = 183-240 urban adults (Agev1 30-64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v1 2004-2009) and 2 (v2 2009-2013), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at vscan 2011-2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER 50 years +393 ± 108] and left occipital pole volume [overall +15.70 ± 3.83 and above poverty 19.0 ± 4.3], findings replicated for 25(OH)D (v2-v1) annualized exposure, which was also linked with greater WMI (fractional anisotropy, FA) in the anterior limb of the internal capsule (ALIC); FWER less then 0.05 [Overall +0.0020 ± 0.0004; Whites +0.0024 ± 0.0004] and in the cingulum (hippocampus) [Overall +0.0016 ± 0.0004]. Only trends were detected for cobalamin exposures (q less then 0.10), while serum folate (v1) was associated with lower mean diffusivity (MD) in ALIC, reflecting greater WMI, overall. Conclusions Among urban adults, serum 25(OH)D status and increase were consistently linked to larger occipital and parietal WM volumes and greater region-specific WMI. Pending longitudinal replication of our findings, randomized controlled trials of vitamin D supplementation should be conducted against brain marker outcomes.As a component of traditional Chinese medicine (TCM), acupuncture has the potential to lower blood pressure (BP) in patients with hypertension. Emerging evidence indicates that the acupuncture-induced inhibition of high BP occurs through the activation of the pathway in the afferent, central, and efferent pathways. An increasing number of studies have demonstrated that acupuncture not only activates distinct brain regions under conditions of hypertension caused by an imbalance between the sympathetic and parasympathetic systems but also modulates neurotransmitters in related brain regions to alleviate the autonomic response. The activity of these pathways can be assessed by injecting agonists or inhibitors or by performing neurotomy. This review focuses on the clinical and mechanistic studies of acupuncture in modulating BP, which might provide a neurobiological foundation for the effects of acupuncture. Although many mechanisms underlying the effects of acupuncture on cardiovascular function have been identified, further investigation is warranted.Biological aging is a complex process involving multiple biological processes. These can be understood theoretically though considering them as individual networks-e.g., epigenetic networks, cell-cell networks (such as astroglial networks), and population genetics. IWP-4 Mathematical modeling allows the combination of such networks so that they may be studied in unison, to better understand how the so-called "seven pillars of aging" combine and to generate hypothesis for treating aging as a condition at relatively early biological ages. In this review, we consider how recent progression in mathematical modeling can be utilized to investigate aging, particularly in, but not exclusive to, the context of degenerative neuronal disease. We also consider how the latest techniques for generating biomarker models for disease prediction, such as longitudinal analysis and parenclitic analysis can be applied to as both biomarker platforms for aging, as well as to better understand the inescapable condition. This review is written by a highly diverse and multi-disciplinary team of scientists from across the globe and calls for greater collaboration between diverse fields of research.The accumulation of extracellular amyloid-beta (Aβ), denoted as senile plaques, and intracellular neurofibrillary tangles (formed by hyperphosphorylated Tau protein) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). The current and most accepted hypothesis proposes that the oligomerization of Aβ peptides triggers the polymerization and accumulation of amyloid, which leads to the senile plaques. Several strategies have been reported to target Aβ oligomerization/polymerization. Since it is thought that Aβ levels in the brain and peripheral blood maintain equilibrium, it has been hypothesized that enhancing peripheral clearance (by shifting this equilibrium towards the blood) might reduce Aβ levels in the brain, known as the sink effect. This process has been reported to be effective, showing a reduction in Aβ burden in the brain as a consequence of the peripheral reduction of Aβ levels. Nanoparticles (NPs) may have difficulty crossing the blood-brain barrier (BBB), initially due to their size.