Transport Mechanism Research Articles

Identification of reversible OATP1B1 and time-dependent CYP3A4 inhibition as the major risk factors for drug-induced cholestasis (DIC).

Hepatic bile acid regulation is a multifaceted process modulated by several hepatic transporters and enzymes. Drug-induced cholestasis (DIC), a main type of drug-induced liver injury (DILI), denotes any drug-mediated condition in which hepatic bile flow is impaired. Our ability in translating preclinical toxicological findings to human DIC risk is currently very limited, mainly due to important interspecies differences. Accordingly, the anticipation of clinical DIC with available in vitro or in silico models is also challenging, due to the complexity of the bile acid homeostasis. Herein, we assessed the in vitro inhibition potential of 47 marketed drugs with various degrees of reported DILI severity towards all metabolic and transport mechanisms currently known to be involved in the hepatic regulation of bile acids. The reported DILI concern and/or cholestatic annotation correlated with the number of investigated processes being inhibited. Furthermore, we employed univariate and multivariate statistical methods to determine the important processes for DILI discrimination. We identified time-dependent inhibition (TDI) of cytochrome P450 (CYP) 3A4 and reversible inhibition of the organic anion transporting polypeptide (OATP) 1B1 as the major risk factors for DIC among the tested mechanisms related to bile acid transport and metabolism. These results were consistent across multiple statistical methods and DILI classification systems applied in our dataset. We anticipate that our assessment of the two most important processes in the development of cholestasis will enable a risk assessment for DIC to be efficiently integrated into the preclinical development process.

A Review: Application of Doped Hydrogenated Nanocrystalline Silicon Oxide in High Efficiency Solar Cell Devices.

Due to the unique microstructure of hydrogenated nanocrystalline silicon oxide (nc-SiOx:H), the optoelectronic properties of this material can be tuned over a wide range, which makes it adaptable to different solar cell applications. In this work, the authors review the material properties of nc-SiOx:H and the versatility of its applications in different types of solar cells. The review starts by introducing the growth principle of doped nc-SiOx:H layers, the effect of oxygen content on the material properties, and the relationship between optoelectronic properties and its microstructure. A theoretical analysis of charge carrier transport mechanisms in silicon heterojunction (SHJ) solar cells with wide band gap layers is then presented. Afterwards, the authors focus on the recent developments in the implementation of nc-SiOx:H and hydrogenated amorphous silicon oxide (a-SiOx:H) films for SHJ, passivating contacts, and perovskite/silicon tandem devices.

Ion transport mechanisms in covalent organic frameworks: implications for technology.

Covalent organic frameworks (COFs) have emerged as promising materials for ion conduction due to their highly tunable structures and excellent electrochemical stability. This review paper explores the mechanisms of ion conduction in COFs, focusing on how these materials facilitate ion transport across their ordered structures, which is crucial for applications such as solid electrolytes in batteries and fuel cells. We discuss the design strategies employed to enhance ion conductivity, including pore size optimization, functionalization with ionic groups, and the incorporation of solvent molecules and salts. Additionally, we examine the various applications of ion-conductive COFs, particularly in energy storage and conversion technologies, highlighting recent advancements and future directions in this field. This review paper aims to provide a comprehensive overview of the current state of research on ion-conductive COFs, offering insights into their potential to design highly ion-conductive COFs considering not only fundamental studies but also practical perspectives for advanced electrochemical devices.

Development of Lead‐Free Defect Brownmillerite Perovskite Ceramic LiBiFeMnO5 Solid Solution for Electronic Devices

This article reports the fabrication (synthesis) and characterizations (structural, microstructural topographic surface, dielectric, transport, impedance, current–voltage, and resistive properties) of a complex lead‐free defect perovskite material of composition LiBiFeMnO5. A preliminary structural investigation of the X‐ray diffraction pattern using N‐TREOR09 methods shows monoclinic symmetry. The scanning electron microscopic spectrum examines the sample's microstructural topographic surface, fractal study, and roughness (using the standard ISO25178). The analysis of Maxwell–Wagner dielectric dispersion, relaxation, and transport mechanisms is investigated utilizing dielectric, impedance, and conductivity spectrum accumulated within the experimental frequency of (1 kHz–1 MHz) at different temperatures (30–500 °C). A nonoverlapping small polaron tunneling conduction mechanism and correlated barrier hopping mechanism in the material have helped to understand its conduction phenomena. The Ohmic and space–charge limited conduction mechanisms are investigated by the slope of the logarithmic electric field (E) and current density (J). The thermistor constant (β) is determined to be 1982.87. The temperature coefficient of resistance is found to be −0.00419, which may be suitable for negative temperature coefficient thermistors, sensors, and other related devices.

Implementing the finite element numerical approach to optimize thermosolutal convection (TSC) energy imparted by discrete heat and solute sources in generalized Newtonian fluid flow in square enclosure

AbstractMesmerizing utilizations of thermosolutal convection (TSC) have been found in metallurgical and petrochemical procedures, crystal growth, thermal exchangers, nuclear waste disposal, and building environment control. In the current study, we considered three heat and solute sources on the left boundary of the cavity, which raises the significance of studying multiple chemical and civil engineering phenomena. Therefore, the prime motivation to commence this work is to attain the optimization of thermosolutal attributes characterized by non-Newtonian (power–law) liquid in the presence of installed sources. For this purpose, the natural convective flow governed by the nonpersistent impact of buoyancy forces is encompassed in the square enclosure. In addition to the source location, the vertical boundaries are considered to be cold, whereas the horizontal boundaries are kept insulated. Owing to the free convective flow, no compositional and thermal gradients are induced by lid movement, and all walls are prescribed with no-slip constraints. To examine the transport mechanism, structuring of problem is attained in the form of dimensional governing expressions by employing conservation laws. Subsequently, constitutive equations in a dimensionless format are accessed through similar variables. The finite element approach is employed to find the solution using COMSOL Multiphysics software. The deviations in the thermal and solutal fields are examined against the involved physical parameters by illustrating graphs and tables. Quantities of interest, such as the mean Nusselt and Sherwood numbers, are also computed against sundry parameters. The assurance of the computed results is validated by constructing a comparison with published studies. A grid sensitivity test is also executed to ensure the credibility of the built-in software (COMSOL). It is observed that the averaged heat and mass flux coefficient diminishes with an elevation in the magnitude of the power-law index (n), irrespective of the change in other involved parameters. The average Sherwood number tends to increase for a positive magnitude of (N) in contrast to negative values of (N). The average heat flux and average mass flux coefficients increase until the Prandtl number (Pr) reaches a value of 5 in shear thinning case at $$Ra\ge {10}^{5},$$ R a ≥ 10 5 , whereas, for n > 1 there is no substantial effect on either the average heat flux coefficient or average mass flux coefficient.

Strong heterologous electron sink outcompetes alternative electron transport pathways in photosynthesis.

Improvement of photosynthesis requires a thorough understanding of electron partitioning under both natural and strong electron sink conditions. We applied a wide array of state-of-the-art biophysical and biochemical techniques to thoroughly investigate the fate of photosynthetic electrons in the engineered cyanobacterium Synechocystis sp. PCC 6803, a blueprint for photosynthetic biotechnology, expressing the heterologous gene for ene-reductase, YqjM. This recombinant enzyme catalyses the reduction of an exogenously added substrate into the desired product by utilising photosynthetically produced NAD(P)H, enabling whole-cell biotransformation. Through coupling the biotransformation reaction with biophysical measurements, we demonstrated that the strong artificial electron sink, outcompetes the natural electron valves, the flavodiiron protein-driven Mehler-like reaction and cyclic electron transport. These results show that ferredoxin-NAD(P)H-oxidoreductase is the preferred route for delivering photosynthetic electrons from reduced ferredoxin and the cellular NADPH/NADP+ ratio as a key factor in orchestrating photosynthetic electron flux. These insights are crucial for understanding molecular mechanisms of photosynthetic electron transport and harnessing photosynthesis for sustainable bioproduction by engineering the cellular source/sink balance. Furthermore, we conclude that identifying the bioenergetic bottleneck of a heterologous electron sink is a crucial prerequisite for targeted engineering of photosynthetic biotransformation platforms.

Sediment Transport Mechanism and Provenance of Unconsolidated Sediments in Opak River Channel, Yogyakarta, Indonesia

This study focuses on the Opak River, which crosses administratively through two regencies, Sleman and Bantul. This research aims to reveal the sedimentation mechanism and provenance of Opak River sediment based on textural and sedimentary composition. Sediment samples were collected from ten points along the river channel, spanning from upstream to downstream. Granulometric and grain morphology analysis were conducted which the followed by QFL analysis wherein the presence of light detrital minerals (quartz, feldspar, lithic) was observed. The sediment texture of Opak River Channel generally consists of coarse-grained sand, poorly sorted, with varying degrees of roundness and sphericity, which are angular to sub-rounded and intermediate to sub-equant, respectively. Opak River sediment predominantly comprises Feldspar (20-48%), Quartz (4-17,9%) and Lithic (13,5-19,6%) which implies arkose-lithic arkose type. The sedimentation process in Opak River is mainly driven by the traction process, which is indicated by a 48-79% traction fraction on the probability log curve. Based on QFL analysis, it is inferred that the Opak River sediment originated tectonically derived from a magmatic arc setting, specifically a transitional arc subtype. The primary sediment source could have been derived from Mount Merapi with a potentially strong influence by the Oyo River, especially in the downstream of Opak River.

Turbulence-reduced high-performance scenarios in Wendelstein 7-X

In the Wendelstein 7-X (W7-X) stellarator, turbulence is the dominant transport mechanism in most discharges. This leads to a ‘clamping’ of ion temperature over a wide range of heating power, predominantly flat density profiles where hollow profiles driven by neoclassical thermo-diffusion would be expected and by rapid impurity transport in injection experiments. Significantly reduced turbulent transport is observed in the presence of strong core density gradients found transiently after core pellet injection and irregularly after boronisation or boron pellet injection. Density peaking is also achieved in a controlled manner in purely neutral beam heated discharges where particle transport analysis reveals an abrupt reduction in the main-ion particle flux leading to significant density profile peaking not explained by the NBI particle source alone. The plasmas exhibit a heat diffusivity of around χ=0.25±0.1m2 s−1 at mid radius, a factor of around 4 lower than ECRH dominated discharges. Despite the improved confinement, the achieved ion temperature is limited by broader heat deposition and the lower power-per-particle given the higher density. This is overcome with limited reintroduction of ECRH power, where the low heat diffusivity diffusivity is maintained, the density rise supressed and ion temperatures above the clamping limit are achieved. The applicability of these plasmas for a high performance scenario on transport relevant time scales is assessed, including initial predictions for planned heating upgrades of W7-X, based on a range of assumptions about particle transport.

Anticancer Effect of PtIIPHENSS, PtII5MESS, PtII56MESS and Their Platinum(IV)-Dihydroxy Derivatives against Triple-Negative Breast Cancer and Cisplatin-Resistant Colorectal Cancer

Development of resistance to cisplatin, oxaliplatin and carboplatin remains a challenge for their use as chemotherapies, particularly in breast and colorectal cancer. Here, we compare the anticancer effect of novel complexes [Pt(1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO3)2 (PtIIPHENSS), [Pt(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO3)2 (PtII5MESS) and [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO3)2 (PtII56MESS) and their platinum(IV)-dihydroxy derivatives with cisplatin. Complexes are greater than 11-fold more potent than cisplatin in both 2D and 3D cell line cultures with increased selectivity for cancer cells over genetically stable cells. ICP-MS studies showed cellular uptake occurred through an active transport mechanism with considerably altered platinum concentrations found in the cytoskeleton across all complexes after 24 h. Significant reactive oxygen species generation was observed, with reduced mitochondrial membrane potential at 72 h of treatment. Late apoptosis/necrosis was shown by Annexin V-FITC/PI flow cytometry assay, accompanied by increased sub-G0/G1 cells compared with untreated cells. An increase in S and G2+M cells was seen with all complexes. Treatment resulted in significant changes in actin and tubulin staining. Intrinsic and extrinsic apoptosis markers, MAPK/ERK and PI3K/AKT activation markers, together with autophagy markers showed significant activation of these pathways by Western blot. The proteomic profile investigated post-72 h of treatment identified 1597 MDA−MB−231 and 1859 HT29 proteins quantified by mass spectroscopy, with several differentially expressed proteins relative to no treatment. GO enrichment analysis revealed a statistically significant enrichment of RNA/DNA-associated proteins in both the cell lines and specific additional processes for individual drugs. This study shows that these novel agents function as multi-mechanistic chemotherapeutics, offering promising anticancer potential, and thereby supporting further research into their application as cancer therapeutics.

Targeting zincosomes to unveil lysosomal zinc ion dynamics and their role in exacerbating Alzheimer's pathology

Maintaining lysosomal zinc (Zn2+) homeostasis is crucial for cellular functionality, with its dysregulation implicated in the progression of neurodegenerative disorders, notably Alzheimer's disease (AD). The paucity of effective tools for precise lysosomal Zn2+ visualization has been a significant barrier to elucidating its role in AD. In response, a highly sensitive and selective novel fluorescent probe based on a salicylaldehyde Schiff base derivative, SSb, was developed to visualize Zn2+ dynamics. Our findings unveil a previously uncharacterized Zn2+ transport mechanism via zincosomes, highlighting their engulfment by mitochondria during autophagy, facilitated by SSb. Significantly, Zn2+ levels were found to be elevated in the brains of AD model mice, associated with amyloid-β (Aβ) deposits. Additionally, our study indicates an abnormal activation of autophagy in AD models, suggesting that Zn2+ increment may exacerbate AD pathology by fostering Aβ deposition and toxicity. This investigation provides valuable insights into Zn2+ homeostasis and its impact on AD, laying the groundwork for novel diagnostic and therapeutic avenues in combating AD, further reflecting the interdisciplinary nature of chemical engineering and biomedical research.

Exploring superionic conduction in lithium oxyhalide solid electrolytes considering composition and structural factors

Lithium (Li) oxyhalides have emerged as promising solid electrolyte candidates for all-solid-state batteries (ASSBs) due to their superior ionic conductivity and excellent cathode capability. However, the mechanism of Li transport in oxyhalides has remained unclear due to the complex nature of these compounds, which often comprise multiple phases such as crystalline and amorphous structures. Herein, a first-principles study using density functional theory and ab initio molecular dynamic simulation is performed to gain a theoretical insight into the structural behavior and conduction pathway in oxyhalide electrolytes. Li2.5ZrCl5.5O0.5 electrolyte, as a case of study, is comprehensively investigated by considering various phases. It’s revealed that the P3̅m1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\rm{P}}\\bar{3}{\\rm{m}}1$$\\end{document} phase is energetically more stable and exhibits one order of magnitude higher Li conductivity compared to the C2/m phase among potential crystalline phases (1.63 mS cm−1 versus 0.24 mS cm−1 at room temperature). Interestingly, an amorphous phase with even higher ionic conductivity (~40 mS cm−1) can be generated by creating LiCl-deficient Li-Zr-O-Cl compounds. The remarkably high ionic conductivity suggests that the amorphous structure is likely the dominant conducting pathway, facilitating fast Li transport due the weak bonding between Li and other atoms. Cl anion mobility is also observed in the amorphous phase through mean square displacement (MSD) calculation, although further analyses revealed this to be localized vibration. This study sheds light on the nature of oxychloride structures and promotes a deeper understanding of the superionic conduction mechanism in oxychlorides, which will contribute to the development of advanced solid electrolytes and ASSBs.

Experimental and numerical simulation research on the transport process of bubble clusters in aeration system

Improving gas-liquid mass transfer efficiency in aeration systems contributes to energy savings, cost reduction, and enhanced efficiency in wastewater treatment. However, due to the complex nonlinear interactions among bubbles in turbulence, understanding the transport mechanisms of non-uniform bubble clusters in turbulence remains unclear. This study employs a combined approach of experimental research and numerical simulations to investigate the shape, diameter distribution, trajectory, and velocity of bubbles under different aeration port sizes and flow rates. The diameter distribution of bubble clusters exhibits a bimodal distribution. Bubble trajectories during ascent mainly exhibit two types of motion patterns: “Z” shaped and linear. Increasing aeration port size and flow rate both lead to an increase in the maximum bubble diameter. Higher initial flow rates and smaller port sizes induce greater lateral velocity fluctuations in bubbles. The proposed numerical simulation method serves as a reference for simulating the transport of non-uniform bubble clusters.

A highly-selective biomimetic potassium channel

Abstract Reproducing the outstanding selectivity achieved by biological ion channels in artificial channel systems can revolutionize applications ranging from membrane filtration to single-molecule sensing technologies, but achieving this goal remains a challenge. Herein, inspired by the selectivity filter structure of the KcsA potassium channel, we propose a design of biomimetic potassium nanochannels by functionalizing the wall of carbon nanotubes with an array of arranged carbonyl oxygen atoms. Our extensive molecular dynamics simulations show that the biomimetic nanochannel exhibits a high K+ permeation rate and meanwhile a high K+/Na+ selectivity ratio. The free energy calculations suggest that the low Na+ permeability is the result of the higher energy barrier for Na+ than K+ at the channel entrance and ion binding sites. In addition, reducing the number of ion binding sites leads to an increase in the permeation rate but a decrease in the selectivity. These findings not only hold promise for the design of high-performance membranes but also help understand the mechanism of selective ion transport in biological ion channels.

Transport characteristic evaluation of runaway electrons in an ITER disruption simulation

In previous studies, it has been observed that the transport of energetic electrons decreases with increasing energy. This observation is a global and long-time-scale result, attributed to the space-averaged perturbations. In this work, we focus on the local and instantaneous transport characteristics of runaway electrons (REs) during the phase of tokamak disruption, with REs speeds close to the speed of light. To simulate the dynamics of REs, we utilize a particle tracing code called PTC. By coupling PTC with the MHD code JOREK, we are able to study the energy and spatial dependence of RE transport. Our investigations reveal that the finite orbit width (FOW) effect plays an important role in RE transport. This effect is influenced by the relative direction of the electron drift and the magnetic field line. Specifically, the FOW effect strengthens the transport when the drift direction aligns with the deflecting direction of the field line. And we compare the transport profiles among three time slices: at the beginning of the thermal quench, during the thermal quench, and at the beginning of the current quench. In this ITER disruption simulation, the perturbation scale is strong and δB/B is up to 0.05 at developed thermal quench stage. It is reasonable that the influence of FOW effect on transport is less than that of magnetic perturbation even if the energy of REs is about hundreds MeV and the orbit width is equal to or greater than the perturbation length. These analyses provide insights into the mechanisms of RE transport based on magnetic perturbations.

A CFD-DEM investigation into hydraulic transport and retardation response characteristics of drainage pipeline siltation using intelligent model

Siltation of drainage pipelines is a major disaster-causing factor in urban flooding. Owing to critical bed shear stress and the possibility of settlement at the bottom of pipes, there are significant nonlinear differences in the hydraulic transport and retardation response characteristics of siltation particles under different initial flow velocities, siltation degrees, and siltation lengths. Studies on siltation in drainage pipelines lack a comprehensive understanding of the intricate coupling dynamics between siltation particles and water flow, and the regularity governing the siltation transport behaviour under varying water flow conditions remains unclear. To solve these problems, this study constructs computational fluid dynamics and discrete element (CFD-DEM) coupling method and adaptive penalty model for pipeline deposition based on probabilistic settlement function, adaptive genetic algorithm, and bidirectional long short-term memory neural network (PSF-AGA-BLSTM). A three-dimensional transient hydraulic model of pipeline siltation was adopted to clarify the critical bed shear stress of the silt particles, after which an adaptive genetic algorithm with a probability settlement function as fitness was constructed to generate a numerous silt particle sample sets with settlement result labels. Adaptive genetic algorithms were combined with bidirectional long short-term memory neural networks to establish a spatiotemporal adaptive penalisation mechanism for pipeline silt particle transport. The simulation model based on PSF-AGA-BLSTM and CFD-DEM was analysed using simulation and scale tests and was found to have strong robustness and reliability. The results showed that the effects of siltation degree, flow rate, and siltation length on the transport of silt particles were all non-negligible; when the siltation degree exceeded 0.2, the siltation degree had a more significant effect on particle transport than siltation length and flow rate. The transport of silt particles occurred in two phases, rapid growth and steady growth under erosion by water flow. The rate of change in silt length accounted for up to 45% of the reason for silt nudging and silt spreading. The study clarified the hydraulic transport law of silt particles and analyzed the effect of different influencing factors. These efforts provide technical support for subsequent pipe cleaning and maintenance as well as flood prevention and mitigation.

Dynamic Second Harmonic Imaging of Proton Translocation Through Water Needles in Lipid Membranes.

Proton translocation through lipid membranes is a fundamental process in the field of biology. Several theoretical models have been developed and presented over the years to explain the phenomenon, yet the exact mechanism is still not well understood. Here, we show that proton translocation is directly related to membrane potential fluctuations. Using high-throughput wide-field second harmonic (SH) microscopy, we report apparently universal transmembrane potential fluctuations in lipid membrane systems. Molecular simulations and free energy calculations suggest that H+ permeation proceeds predominantly across a thin, membrane-spanning water needle and that the transient transmembrane potential drives H+ ions across the water needle. This mechanism differs from the transport of other cations that require completely open pores for transport and follows naturally from the well-known Grotthuss mechanism for proton transport in bulk water. Furthermore, SH imaging and conductivity measurements reveal that the rate of proton transport depends on the structure of the hydrophobic core of bilayer membranes.

Mechanism of Iron Transport in the Triticum aestivum L.–Soil System: Perception from a Pot Experiment

Mechanism of Iron Transport in the Triticum aestivum L.–Soil System: Perception from a Pot Experiment

Charge Transfer Mechanism in Guanine-Based Self-Assembled Monolayers on a Gold Surface.

In this work, we have theoretically determined the one-electron oxidation potentials and charge transfer mechanisms in complex systems based on a self-assembled monolayer of guanine molecules adsorbed on a gold surface through different organic linkers. Classical molecular dynamics simulations were carried out to sample the conformational space of both the neutral and the cationic species. Thus, the redox potentials were determined for the ensembles of geometries through multiscale quantum-mechanics/molecular-mechanics/continuum solvation model calculations in the framework of the Marcus theory and in combination with an additive scheme previously developed. In this context, conformational sampling, description of the environment, and effects caused by the linker have been considered. Applying this methodology, we unravel the phenomena of electric current transport by evaluating the different stages in which charge transfer could occur. The results revealed how the positive charge migrates from the organic layer to the gold surface. Specifically, the transport mechanism seems to take place mainly along a single ligand and driven with the help of the electrostatic interactions of the surrounding molecules. Aside, several self-assembled monolayers with different linkers have been analyzed to understand how the nature of that moiety can tune the redox properties and the efficiency of the transport. We have found that the conjugation between the guanine and the linker, at the same time conjugated to the gold surface, gives rise to a more efficient transport. In conclusion, the established computational protocol sheds light on the mechanism behind charge transport in electrochemical DNA-based biosensor nanodevices.

Charge Transfer Mechanism in Guanine-Based Self-Assembled Monolayers on a Gold Surface.

In this work, we have theoretically determined the one-electron oxidation potentials and charge transfer mechanisms in complex systems based on a self-assembled monolayer of guanine molecules adsorbed on a gold surface through different organic linkers. Classical molecular dynamics simulations were carried out to sample the conformational space of both the neutral and the cationic species. Thus, the redox potentials were determined for the ensembles of geometries through multiscale quantum-mechanics/molecular-mechanics/continuum solvation model calculations in the framework of the Marcus theory and in combination with an additive scheme previously developed. In this context, conformational sampling, description of the environment, and effects caused by the linker have been considered. Applying this methodology, we unravel the phenomena of electric current transport by evaluating the different stages in which charge transfer could occur. The results revealed how the positive charge migrates from the organic layer to the gold surface. Specifically, the transport mechanism seems to take place mainly along a single ligand and driven with the help of the electrostatic interactions of the surrounding molecules. Aside, several self-assembled monolayers with different linkers have been analyzed to understand how the nature of that moiety can tune the redox properties and the efficiency of the transport. We have found that the conjugation between the guanine and the linker, at the same time conjugated to the gold surface, gives rise to a more efficient transport. In conclusion, the established computational protocol sheds light on the mechanism behind charge transport in electrochemical DNA-based biosensor nanodevices.

Cluster of Differentiation 36 (CD36) Preferentially Mediates Intestinal Absorption of Dietary Z-Astaxanthin and Especially 9-Z-Isomer via Higher Binding Affinity.

Variances in the biological functions of astaxanthin geometric isomers (i.e., all-E, Z) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z-astaxanthin, particularly the 9-Z-isomer (47.76%). The absorption rate and permeability of Z-astaxanthin surpassed that of the all-E-isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo-N-succinimidyl oleate significantly reduced the absorption of Z-astaxanthin in the mouse duodenum and jejunum, especially the 9-Z-isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9-Z-astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.