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Epithelioid hemangioma is a rare, histologically benign but locally aggressive primary vascular neoplasm that can rarely arise in bone. Mainstay treatment is surgical resection or curettage with bone grafting. We report a novel multidisciplinary, joint-sparing treatment approach for an epithelioid hemangioma of bone arising in the acetabulum causing severe thinning of the subchondral bone plate. After 4 sessions of transarterial bland particle and ethanol embolization, the resultant increased ossification of the tumor allowed preservation of the articular surface during surgical resection. Imaging follow-up 14 months after surgical resection showed no evidence of recurrence and continued ossification of the portions of the lesion treated only with embolization.

The potential of rideshare services to facilitate timely radiation therapy (RT), especially for resource-limited patients, is understudied.Patients (N=63) who received 73 courses of RT (1,513 fractions) and utilized free hospital-provided rideshare service (537 rides) were included in this retrospective study. A multi-dimensional analysis was conducted including a comparison of demographic, disease characteristics, and treatment completion data; a revenue analysis to evaluate the financial impact of rideshare services; and a geospatial analysis to evaluate community-level characteristics of patients.Median age was 59; the majority was female (56%), self-identified as Black or African American (56%), not working (91%), not partnered (83%), high school educated or less (78%), and insured with Medicaid (51%). Geospatial analysis reveals that patients lived in communities with significantly higher rates of resource deprivation. Median rideshare distance was 6.4 miles (IQR 3.4-11.2) with a median cost of $13.04 per rideshare (IQR 9-19). Of the rideshare-facilitated treatments, 100% were completed, with an overall course completion rate of 97.3% compared to 85.4% for those who did not use rideshare (p=0.001); 2 patients discontinued RT for reasons unrelated to transportation. High rideshare utilization (N=32), defined as utilization ≥ 45% of the treatment course, was associated with significantly shorter treatment courses and lower radiation doses compared to low rideshare utilization (p=0.04). Total rideshare cost for high utilizers/whole cohort was $11,589/$16,895, facilitating an estimated revenue of $401,952/$1,175,119.Free hospital-provided rideshare service is economically feasible and associated with high RT completion rates. It may help enhance quality radiation care for those who come from resource-limited communities.

The modulation of electron density at the Pyridoxal 5'-phosphate (PLP) catalytic center, because of charge transfer across the α-helix/PLP interface, is the determining factor for the enzymatic activities in the human Cystathionine β-Synthase (hCBS) enzyme. Applying density functional theory calculations, in conjunction with the real space density analysis, we investigated the charge density delocalization across the entire heme-α-helix-PLP electron communication channels. The electron delocalization due to hydrogen bonds at the heme/α-helix and α-helix/PLP interfaces are found to be extended over a very long range, as a result of redistribution of electron densities of the cofactors. Moreover, the internal hydrogen bonds of α-helix that are crucial for its secondary structure also participate in the electron redistribution through the structured hydrogen-bond network. α-Helix is found to accumulate the electron density at the ground state from both of the cofactors and behaves as an electron reservoir for catalytic reaction at the electrophilic center of PLP.

Chain collapse in synthetic polymers is an excellent approach for mimicking the natural self-folding process that imparts structural control, leading to attractive compartmental applications, e.g. drug delivery. In this regard, water-soluble and thermo-responsive polyacrylamide polymers CP1–2 with photodimerizable coumarin moieties grafted into the backbone are employed to design polymeric nanoparticles. The chain collapse can be efficiently controlled using dual response strategies involving photodimerization under UVB light (λmax = 320 nm) as well as host–guest interaction by the addition of a bis-β-CD host. The aggregation of the nanoparticles is controlled by the interplay of a lower critical solution temperatures (LCST) that can be tuned as a result of photodimerization and host–guest interaction. Further, sequential folding of the polymers is demonstrated by the addition of the host molecule followed by exposure to UVB irradiation. Such multi-stimuli-responsive compaction of size with synergistic control of non-covalent and dynamic covalent interaction and tuning of LCST render the system suitable for compartmental loading and sustainable/burst release of hydrophilic and hydrophobic cargos e.g. rhodamine B dye and the drug ibuprofen under homeostasis control.

The modulation of electron density at the Pyridoxal 5-phosphate (PLP) catalytic center, due to charge transfer across the α-Helix-PLP interface, is the determining factor for the enzymatic activities in the human Cystathionine β-Synthase (hCBS) enzyme. Applying density-based first-principle calculations in conjunction with the real space density analysis, we investigated the charge density delocalization across the entire Heme-α-Helix-PLP electron communication channels. The hydrogen bonds at the interfaces, i.e. Heme-α-Helix and α-Helix-PLP interfaces, are found to play the pivotal role in bi-directional electron transfer towards the α-Helix. Moreover, the internal hydrogen bonds of α-Helix that are crucial for its secondary structure also actively participate in the electron redistribution through the structured hydrogen bond network. α-Helix is found to accumulate the electron density at the ground state from both the cofactors and behaves as an electron reservoir for catalytic reaction at the electrophilic center of PLP.

Human cystathionine β-synthase (hCBS) is a Heme-containing, unique pyridoxal 5'-phosphate (PLP) dependent enzyme. CBS catalyzes the bio-chemical condensation reactions in the transsulfuration pathway. The role of Heme in the catalytic activities of the hCBS enzyme is still unknown, even though various experimental studies indicated its participation in the bi-directional electronic communication with the PLP center. The hypothesis is, Heme acts as an electron density reservoir for the catalytic reaction center rather than a redox electron source. In this work, we have investigated

Human cystathionine β-synthase (hCBS) is a Heme containing unique pyridoxal 5’-phosphate (PLP) dependent enzyme that catalyzes the bio-chemical condensation reactions in the transsulfuration pathway. The role of Heme in the catalytic activities of enzyme has not yet been understood completely, even though various experimental studies have indicated its participation in the bi-directional electronic communication with the PLP center. Most probably Heme acts as the electron density reservoir for the catalytic reaction center but not as a redox electron source. Here, in this work, we investigated In Silico dynamical aspects of the bi-directional communications by performing classical molecular dynamics (MD) simulations upon developing the necessary force field parameters for the cysteine and histidine bound hexa-coordinated Heme. The comparative aspects of electron density overlap across the communicating pathways are also explored adopting the density functional theory (DFT) in conjunction with the hybrid exchange-correlation functional for the CSBWT (wild-type) and CBSR266K (mutated) case. The atomistic MD simulations and subsequent explorations of the electronic structures not only confirm the reported observations but provide an in-depth mechanistic understating of how the non-covalent hydrogen bonding interactions with Cys52 control such long-distance communication. Our study also provides a convincing answer to the reduced enzymatic activities in the R266K hCBS in comparison to the wild-type enzymes. We further realized that the difference in hydrogen-bonding patterns, as well as salt-bridge interactions, play a pivotal role in such long distant bi-directional communications.

Human cystathionine β-synthase (hCBS) is a Heme-containing, unique pyridoxal 5’-phosphate (PLP) dependent enzyme. CBS catalyzes the bio-chemical condensation reactions in the transsulfuration pathway. The role of Heme in the catalytic activities of the hCBS enzyme is still unknown, even though various experimental studies indicated its participation in the bi-directional electronic communication with the PLP center. The hypothesis is, Heme acts as an electron density reservoir for the catalytic reaction center rather than a redox electron source. In this work, we have investigated In Silico dynamical aspects of the bi-directional communications by performing classical molecular dynamics (MD) simulations upon developing the necessary force field parameters for the cysteine and histidine bound hexa-coordinated Heme. The comparative aspects, of electron density overlap across the communicating pathways, were investigated adopting the Density Functional Theory (DFT) in conjunction with the hybrid exchange-correlation functional for the CBSWT (wild-type) and CBSR266K (mutated) enzymes. The molecular dynamics simulations and subsequent explorations of the electronic structures confirm the reported observations. It also provides an in-depth mechanistic understanding of how the non-covalent hydrogen bonding interactions with Cys52 control such long-distance communication. Our study also provides a convincing answer to the reduced enzymatic activities in the R266K mutated hCBS compared to the wild-type enzymes. The difference in hydrogen-bonding patterns and salt-bridge interactions play the pivotal roles in such long distant bi-directional communications. Communicated by Ramaswamy H. Sarma

Bacterial microcompartments (MCPs) are polyhedral organelles containing an enzyme cluster wrapped inside a protein shell and carry out specific enzyme reactions in bacteria. These organelles have been explored meticulously using genetic, structural, and biochemical tools; however, their application in material science has not been explored much. In this study, we have used the external shell surface of MCP as a scaffold for the fabrication of gold nanoparticles displayed in 3D. This resulted in the formation of a protein scaffolded gold nanoparticle shell enclosing an active enzyme cluster. The surface scaffolded gold nanoparticles demonstrated standard catalysis, while the internal enzyme cluster of the MCPs demonstrated no loss in activity due to this fabrication. Under ambient conditions for in vitro inorganic reaction, the shell proteins sturdily maintain the barrier between the luminal enzyme and the surface inorganic catalysts and preserve the functionality of the core enzyme cluster. The MCP-AuNPs ...