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Nitisinone (NTBC) is used in the treatment of disorders affecting the tyrosine pathway, including hereditary tyrosinemia type I, alkaptonuria, and neuroblastoma. An inappropriate dosage of this therapeutic drug causes side effects; therefore, it is necessary to develop a rapid and sensitive method to monitor the content of NTBC in patients’ blood. This study aimed to develop anew polymeric sorbent containing β-cyclodextrin (β-CD) derivatives grafted on silica gel to effectively extract NTBC from model physiological fluids. The inclusion complex formed between β-CD and NTBC was examined by proton nuclear magnetic resonance spectroscopy. The novel sorbents with derivatives of β-CD were prepared on modified silica gel using styrene as a comonomer, ethylene glycol dimethacrylate as a crosslinking agent, and 2,2′-azo-bis-isobutyronitrile as a polymerization initiator. The obtained products were characterized via Fourier transform infrared spectroscopy and then used as sorbents as part of a solid phase extraction technique. High NTBC recovery (70%indicated that the developed polymeric sorbent may be suitable for extracting this compound from patients’ blood samples.

Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. (2018), Bedussi et al. (2018)). The oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Using computational fluid dynamics, we computed the CSF velocity and pressure in a PVS surrounding a cerebral artery subject to different forces, representing arterial wall expansion, systemic CSF pressure changes and rigid motions of the artery. The arterial wall expansion generated velocity amplitudes of 60–260 μ m/s, which is in the upper range of previously observed values. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5 μ m/s), though reaching up to 7 μ m/s for non-physiological PVS lengths. In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30 μ m/s. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS. Our study demonstrates that the combination of arterial wall expansion, rigid motions and a static CSF pressure gradient generates net and oscillatory PVS flow, quantitatively comparable with experimental findings. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined.

Alzheimer’s disease and related dementias (ADRD) present a significant global disease burden that is only expected to grow in the future. As such, there is a need to develop and investigate biomarkers that identify individuals at risk of developing ADRD with the goal of providing early interventions and treatments. Non-human primate (NHP) models of neurodegeneration present opportunities to examine such biomarkers in a preclinical model with the ability to control several confounding factors present in research with humans. Baboons naturally develop several ADRD-related neuropathologies that humans also exhibit, including age-related tau and amyloid deposition. However, to our knowledge, there are no data characterizing fluid biomarkers relevant to neurodegeneration or ADRD in baboons. We collected plasma (N = 139) and cerebrospinal fluid (CSF, N = 44) from captive baboons ranging in age from 3–19 years old. We characterized biomarkers as a function of age, sex, and rearing status in baboons using a bead-based bioplex human assay (Thermo Fisher Scientific’s Neuroscience 18-Plex Human ProcartaPlex™ Panel). Fluid biomarkers were more detectable in CSF compared to plasma. Additionally, while sex and rearing did not significantly predict biomarkers in baboons, age significantly predicted levels of eight of the 12 biomarkers detected in the assay. Linear regressions showed that CSF levels of total tau, pTau181, NGF-beta, GFAP, NF-H, and S100B were higher in older baboons, as were plasma levels of NGF-beta. Lastly, older baboons showed a higher incidence of co-occurrence of multiple biomarkers as measured in CSF, but not in plasma. These data show that baboons exhibit age-dependent changes in biomarkers used in humans for clinical screening, diagnosis, and prognosis of ADRD, thereby further demonstrating the value of baboons as a model of aging and, possibly, ADRD.

The organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

Since its discovery 1 , 2 , the deep-sea glass sponge Euplectella aspergillum has attracted interest in its mechanical properties and beauty. Its skeletal system is composed of amorphous hydrated silica and is arranged in a highly regular and hierarchical cylindrical lattice that begets exceptional flexibility and resilience to damage 3 – 6 . Structural analyses dominate the literature, but hydrodynamic fields that surround and penetrate the sponge have remained largely unexplored. Here we address an unanswered question: whether, besides improving its mechanical properties, the skeletal motifs of E. aspergillum underlie the optimization of the flow physics within and beyond its body cavity. We use extreme flow simulations based on the ‘lattice Boltzmann’ method 7 , featuring over fifty billion grid points and spanning four spatial decades. These in silico experiments reproduce the hydrodynamic conditions on the deep-sea floor where E. aspergillum lives 8 – 10 . Our results indicate that the skeletal motifs reduce the overall hydrodynamic stress and support coherent internal recirculation patterns at low flow velocity. These patterns are arguably beneficial to the organism for selective filter feeding and sexual reproduction 11 , 12 . The present study reveals mechanisms of extraordinary adaptation to live in the abyss, paving the way towards further studies of this type at the intersection between fluid mechanics, organism biology and functional ecology. High-performance hydrodynamic simulations show that the skeletal structure of the deep-sea sponge Euplectella aspergillum reduces the hydrodynamic stresses on it, while possibly being beneficial for feeding and reproduction.

The impact of drug delivery and particulate matter exposure on the human respiratory tract is influenced by various anatomical and physiological factors, particularly the structure of the respiratory tract and its fluid dynamics. This study employs computational fluid dynamics (CFD) to investigate airflow in two 3D models of the human air conducting zone. The first model uses a combination of CT-scan images and geometrical data from human cadaver to extract the upper and central airways down to the ninth generation, while the second model develops the lung airways from the first Carina to the end of the ninth generation using Kitaoka’s deterministic algorithm. The study examines the differences in geometrical characteristics, airflow rates, velocity, Reynolds number, and pressure drops of both models in the inhalation and exhalation phases for different lobes and generations of the airways. From trachea to the ninth generation, the average air flowrates and Reynolds numbers exponentially decay in both models during inhalation and exhalation. The steady drop is the case for the average air velocity in Kitaoka’s model, while that experiences a maximum in the 3rd or 4th generation in the quasi-realistic model. Besides, it is shown that the flow field remains laminar in the upper and central airways up to the total flow rate of 15 l/min. The results of this work can contribute to the understanding of flow behavior in upper respiratory tract. Graphical Abstract

Climate change exposes vegetation to unusual drought, causing declines in productivity and increased mortality. Drought responses are hard to anticipate because canopy transpiration and diffusive conductance (G) respond to drying soil and vapor pressure deficit (D) in complex ways. A growing database of hydraulic traits, combined with a parsimonious theory of tree water transport and its regulation, may improve predictions of at-risk vegetation. The theory uses the physics of flow through soil and xylem to quantify how canopy water supply declines with drought and ceases by hydraulic failure. This transpiration ‘supply function’ is used to predict a water ‘loss function’ by assuming that stomatal regulation exploits transport capacity while avoiding failure. Supply–loss theory incorporates root distribution, hydraulic redistribution, cavitation vulnerability, and cavitation reversal. The theory efficiently defines stomatal responses to D, drying soil, and hydraulic vulnerability. Driving the theory with climate predicts drought-induced loss of plant hydraulic conductance (k), canopy G, carbon assimilation, and productivity. Data lead to the ‘chronic stress hypothesis’ wherein > 60% loss of k increases mortality by multiple mechanisms. Supply–loss theory predicts the climatic conditions that push vegetation over this risk threshold. The theory's simplicity and predictive power encourage testing and application in large-scale modeling.

The present analysis deals with the entropy analysis of the blood flow through an anisotropically tapered arteries under the suspension of magnetic Zinc-oxide (ZnO) nanoparticles (NPs). The Jeffrey fluid model is contemplated as blood that is electrically conducting and incompressible. The lubrication approach is used for the mathematical modeling. The second law of thermodynamics is used to examine the entropy generation. The exact solutions are obtained against velocity and temperature profile with the use of computational software. The results for Entropy, Velocity, Bejan number, temperature profile, and impedance profile are discussed by plotting the graphs. ZnO-NPs have promising applications in biomedical engineering due to its low toxicity, economically reliable, and excellent biocompatibility. ZnO-NPs also emerged in medicine i.e., antibacterial and anticancer activity, and also beneficial in antidiabetic treatment. The monitoring of the blood temperature in the case of the tapered artery has supreme importance in controlling the temperature of blood in the living environment. The presence of a magnetic field is advantageous to manage and control the blood motion at different temperatures. The present outcomes are enriched to give valuable information for the research scientists in the field biomedical science, who are looking to examine the blood flow with stenosis conditions and also beneficial in treating multiple diseases.

A mathematical model of interstitial fluid flow is developed, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for a predefined tumor geometry. The interstitial fluid pressure and velocity are calculated using a numerical method, element based finite volume. Simulations of interstitial fluid transport in a homogeneous solid tumor demonstrate that, in a uniformly perfused tumor, i.e., one with no necrotic region, because of the interstitial pressure distribution, the distribution of drug particles is non-uniform. Pressure distribution for different values of necrotic radii is examined and two new parameters, the critical tumor radius and critical necrotic radius, are defined. Simulation results show that: 1) tumor radii have a critical size. Below this size, the maximum interstitial fluid pressure is less than what is generally considered to be effective pressure (a parameter determined by vascular pressure, plasma osmotic pressure, and interstitial osmotic pressure). Above this size, the maximum interstitial fluid pressure is equal to effective pressure. As a consequence, drugs transport to the center of smaller tumors is much easier than transport to the center of a tumor whose radius is greater than the critical tumor radius; 2) there is a critical necrotic radius, below which the interstitial fluid pressure at the tumor center is at its maximum value. If the tumor radius is greater than the critical tumor radius, this maximum pressure is equal to effective pressure. Above this critical necrotic radius, the interstitial fluid pressure at the tumor center is below effective pressure. In specific ranges of these critical sizes, drug amount and therefore therapeutic effects are higher because the opposing force, interstitial fluid pressure, is low in these ranges.

It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs. Ablation of hypothalamic stem/progenitor cells in mice leads to ageing-related decreases in physiological parameters and lifespan, and the speed of ageing is partially controlled by these cells through the release of exosomal miRNAs. Hypothalamus controls the speed of ageing Dongsheng Cai and colleagues previously showed that the hypothalamus has a critical role in systemic ageing. Here they observe a substantial loss of hypothalamic stem cells in middle-aged mice. They show in several mouse models that ablation of these cells results in ageing-like physiological changes and a shortened lifespan. Conversely, ageing could be slowed and lifespan extended by transplantation of healthy hypothalamic stem cells into middle aged mice. Hypothalamic stem cells secrete exosomal miRNAs, contributing to a pool of circulating miRNAs in the cerebrospinal fluid that declines with age. These secreted exosomes contribute, at least in part, to a deceleration of ageing. The authors conclude that the speed of ageing is partially controlled by hypothalamic stem cells and their exosomal miRNAs in the cerebrospinal fluid.