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1. Physiologically-Based Pharmacokinetic Modeling of Blood Clearance of Liver Fluorescent Markers for the Assessment of the Degree of Hepatic Ischemia-Reperfusion Injury ^*

   https://doi.org/10.1109/EMBC40787.2023.10340273  

   Monti, Christopher; Audi, Said H; Womack, Justin; Hong, Seung-Keun; Yang, Yongqiang; Kim, Joohyun; Dash, Ranjan K (July 2023, IEEE)

   Abstract— During liver transplantation, ischemia-reperfusion injury (IRI) is inevitable and decreases the overall success of the surgery. While guidelines exist, there is no reliable way to quantitatively assess the degree of IRI present in the liver. Our recent study has shown a correlation between the bile-to-plasma ratio of FDA-approved sodium fluorescein (SF) and the degree of hepatic IRI, presumably due to IRI-induced decrease in the activity of the hepatic multidrug resistance-associated protein 2 (MRP2); however, the contribution of SF blood clearance via the bile is still convoluted with other factors, such as renal clearance. In this work, we sought to computationally model SF blood clearance via the bile. First, we converted extant SF fluorescence data from rat whole blood, plasma, and bile to concentrations using calibration curves. Next, based on these SF concentration data, we generated a “liver-centric”, physiologically-based pharmacokinetic (PBPK) model of SF liver uptake and clearance via the bile. Model simulations show that SF bile concentration is highly sensitive to a change in the activity of hepatic MPR2. These simulations suggest that SF bile clearance along with the PBPK model can be used to quantify the effect of IRI on the activity of MRP2. Clinical Relevance— This study establishes the theory necessary to generate a model for predicting the degree of IRI during liver transplantation. 

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2. The Role of NMDA Receptor Partial Antagonist, Carbamathione, as a Therapeutic Agent for Transient Global Ischemia

   https://doi.org/10.3390/biomedicines11071885  

   Modi, Jigar Pravinchandra; Shen, Wen; Menzie-Suderam, Janet; Xu, Hongyuan; Lin, Chun-Hua; Tao, Rui; Prentice, Howard M; Schloss, John; Wu, Jang-Yen (July 2023, Biomedicines)

   Fregni, F (Ed.)

   Carbamathione (Carb), an NMDA glutamate receptor partial antagonist, has potent neuroprotective functions against hypoxia- or ischemia-induced neuronal injury in cell- or animal-based stroke models. We used PC-12 cell cultures as a cell-based model and bilateral carotid artery occlusion (BCAO) for stroke. Whole-cell patch clamp recording in the mouse retinal ganglion cells was performed. Key proteins involved in apoptosis, endoplasmic reticulum (ER) stress, and heat shock proteins were analyzed using immunoblotting. Carb is effective in protecting PC12 cells against glutamate- or hypoxia-induced cell injury. Electrophysiological results show that Carb attenuates NMDA-mediated glutamate currents in the retinal ganglion cells, which results in activation of the AKT signaling pathway and increased expression of pro-cell survival biomarkers, e.g., Hsp 27, P-AKT, and Bcl2 and decreased expression of pro-cell death markers, e.g., Beclin 1, Bax, and Cleaved caspase 3, and ER stress markers, e.g., CHOP, IRE1, XBP1, ATF 4, and eIF2α. Using the BCAO animal stroke model, we found that Carb reduced the brain infarct volume and decreased levels of ER stress markers, GRP 78, CHOP, and at the behavioral level, e.g., a decrease in asymmetric turns and an increase in locomotor activity. These findings for Carb provide promising and rational strategies for stroke therapy. 

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3. Loss of effective lubricating viscosity is the primary mechanical marker of joint inflammation in equine synovitis

   https://doi.org/10.1002/jor.25793  

   Vishwanath, Karan; Secor, Erica J; Watkins, Amanda; Reesink, Heidi L; Bonassar, Lawrence J (July 2024, Journal of Orthopaedic Research)

   Abstract Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro‐inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well‐established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000‐fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = −0.6 to −0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E₂(PGE₂), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA. 

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4. Observation of Anisotropic Superfluid Density in an Artificial Crystal

   https://doi.org/10.1103/PhysRevLett.131.163401  

   Tao, J.; Zhao, M.; Spielman, I. B. (October 2023, Physical Review Letters)

   We experimentally and theoretically investigate the anisotropic speed of sound of an atomic superfluid (SF) Bose-Einstein condensate in a 1D optical lattice. Because the speed of sound derives from the SF density, this implies that the SF density is itself anisotropic. We find that the speed of sound is decreased by the optical lattice, and the SF density is concomitantly reduced. This reduction is accompanied by the appearance of a zero entropy normal fluid in the purely Bose condensed phase. The reduction in SF density—first predicted [A. J. Leggett, Phys. Rev. Lett. 25, 1543 (1970).] in the context of supersolidity—results from the coexistence of superfluidity and density modulations, but is agnostic about the origin of the modulations. We additionally measure the moment of inertia of the system in a scissors mode experiment, demonstrating the existence of rotational flow. As such we shed light on some supersolid properties using imposed, rather than spontaneously formed, density order. 

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5. Prevalence of Compact Nuclear Radio Emission in Post-merger Galaxies and Its Origin

   https://doi.org/10.3847/1538-4357/ad50a1  

   Walsh, Gregory; Burke-Spolaor, Sarah (August 2024, The Astrophysical Journal)

   Abstract Post-merger galaxies are unique laboratories to study the triggering and interplay of star formation and active galactic nucleus (AGN) activity. Combining new, high-resolution Jansky Very Large Array (VLA) observations with archival radio surveys, we have examined the radio properties of 28 spheroidal post-merger galaxies. We detect 18 radio sources in our post-merger sample and find a general lack of extended emission at (sub)kiloparsec scales, indicating the prevalence of compact, nuclear radio emission in these post-merger galaxies, with the majority (16/18; 89%) characterized as low luminosity. Using multiwavelength data, we determine the origin of the radio emission, discovering 15 new radio AGNs and three radio sources likely associated with star-forming (SF) processes. Among the radio AGNs, almost all are low luminosity (13/15; 87%), inconsistent with a relativistic jet origin. We discover a new dual AGN (DAGN) candidate, J1511+0417, and investigate the radio properties of the DAGN candidate J0843+3549. Five of these radio AGNs are hosted by a SF or SF-AGN composite emission-line galaxy, suggesting that radio AGN activity may be present during periods of SF activity in post-mergers. The low-power jets and compact morphologies of these radio AGNs also point to a scenario in which AGN feedback may be efficient in this sample of post-mergers. Lastly, we present simulated, multifrequency observations of the 15 radio AGNs with the Very Long Baseline Array and the very-long-baseline interferometry capabilities of the Next-Generation VLA to assess the feasibility of these instruments in searches for supermassive black hole binaries. 

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