Large-eddy simulation of aerosol concentrations in a realistic urban environment: Model validation and transport mechanism.

Air pollution in urban environments exhibits large spatial and temporal variations due to high heterogeneous air flow and emissions. To address the complexity of local air pollutant dynamics, a comprehensive large-eddy simulation using the PALM model system v6.0 was conducted. The distribution of flow and vehicle emitted aerosol particles in a realistic urban environment in Malmö, Sweden, was studied and evaluated against on-site measurements made using portable instrumentation on a spring morning in 2021. The canyon transport mechanisms were investigated, and the convective and turbulent mass-transport rates compared to clarify their role in aerosol transport. The horizontal distribution of aerosols showed acceptable evaluation metrics for both mass and number. Flow and pollutant concentrations were more complex than those in idealized street canyon networks. Vertical turbulent mass-transport rate was found to dominate the mass transport process compared with the convective transport rate, contributing more than 70% of the pollutant transport process. Our findings highlight the necessity of examining various aerosol metric due their distinct dispersion behaviour. This study introduces a comprehensive high-resolution modelling framework that accounts for dynamic meteorological and aerosol background boundary conditions, real-time traffic emission, and detailed building features, offering a robust toll for local urban air quality assessment.

Electrostatic Repulsion Facilitated Ion Transport in Covalent-Organic Framework Membranes.

Covalent-organic framework (COF) membranes are increasingly used for many potential applications including ion separation, fuel cells, and ion batteries. It is of central importance to fundamentally and quantitatively understand ion transport in COF membranes. In this study, a series of COF membranes is designed with different densities and arrangements of functional groups and subsequently utilize molecular simulation to provide microscopic insights into ion transport in these membranes. The membrane with a single-sided layer exhibits the highest chloride ion (Cl-) conductivity of 77.2 mS cm-1 at 30 °C. Replacing the single-sided layer with a double-sided layer or changing layer arrangement leads to a decrease in Cl- conductivity up to 33% or 53%, respectively. It is revealed that the electrostatic repulsion between ions serves as a driving force to facilitate ion transport and the positions of functional groups determine the direction of electrostatic repulsion. Furthermore, the ordered pores generate concentrated ions and allow rapid ion transport. This study offers bottom-up inspiration on the design of new COF membranes with moderate density and proper arrangement of functional groups to achieve high ion conductivity.

Transport of glycinin, the major soybean allergen, across intestinal epithelial IPEC-J2 cell monolayers.

Soybean allergen entering the body is the initial step to trigger intestinal allergic response. However, it remains unclear how glycinin, the major soybean allergen, is transported through the intestinal mucosal barrier. The objective of this study was to elucidate the pathway and mechanism of glycinin hydrolysate transport through the intestinal epithelial barrier using IPEC-J2 cell model. Purified glycinin was digested by in vitro static digestion model. The pathway and mechanism of glycinin hydrolysates transport through intestinal epithelial cells were investigated by cellular transcytosis assay, cellular uptake assay, immunoelectron microscopy and endocytosis inhibition assay. The glycinin hydrolysates were transported across IPEC-J2 cell monolayers in a time/dose-dependent manner following the Michaelis equation. Immunoelectron microscopy showed a number of glycinin hydrolysates appeared in the cytoplasm, but no glycinin hydrolysates were observed in the intercellular space of IPEC-J2 cells. The inhibitors, colchicine, chlorpromazine and methyl-ß-cyclodextrin, significantly inhibited the cellular uptake of glycinin hydrolysates. The glycinin hydrolysates crossed IPEC-J2 cell monolayers through the transcellular pathway. Both clathrin- and caveolae-dependent endocytosis were involved in the epithelial uptake of the hydrolysates. These findings provided potential targets for the prevention and treatment of soybean allergy.

Enhanced Sampling Molecular Dynamics Simulations Reveal Transport Mechanism of Glycoconjugate Drugs through GLUT1.

Glucose transporters GLUT1 belong to the major facilitator superfamily and are essential to human glucose uptake. The overexpression of GLUT1 in tumor cells designates it as a pivotal target for glycoconjugate anticancer drugs. However, the interaction mechanism of glycoconjugate drugs with GLUT1 remains largely unknown. Here, we employed all-atom molecular dynamics simulations, coupled to steered and umbrella sampling techniques, to examine the thermodynamics governing the transport of glucose and two glycoconjugate drugs (i.e., 6-D-glucose-conjugated methane sulfonate and 6-D-glucose chlorambucil) by GLUT1. We characterized the specific interactions between GLUT1 and substrates at different transport stages, including substrate recognition, transport, and releasing, and identified the key residues involved in these procedures. Importantly, our results described, for the first time, the free energy profiles of GLUT1-transporting glycoconjugate drugs, and demonstrated that H160 and W388 served as important gates to regulate their transport via GLUT1. These findings provide novel atomic-scale insights for understanding the transport mechanism of GLUT1, facilitating the discovery and rational design of GLUT1-targeted anticancer drugs.

The tilting motion of the central core reveals the transport mechanism of the sarco/endoplasmic reticulum Ca2+-ATPase.

The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) transports two Ca2+ ions per ATP hydrolyzed from the cytoplasm to the lumen. However, how the ATP hydrolysis remotely drives the Ca2+ transport is unclear. In the SERCA1a crystal structures, the ATP hydrolysis is accompanied by the notably increasing tilting angle of the central core (CC) and the Ca2+ transport, and the CC tilting angle dramatically decreases in the E2 to E1 transition. We demonstrated that the significantly increasing tilting motion of the CC drove the Ca2+ release in the molecular dynamics simulation of the R836A variant, and the dramatic spontaneous decrease in the CC tilting angle of the E2 state triggers the restart of the SERCA1a's transport cycle. The repulsion between the phosphorylated D351 and the phosphate groups in ADP triggers the release of ADP from the SERCA1a headpiece. We proposed a novel SERCA transport mechanism in which ATP hydrolysis drives a significant tilting motion of the CC, which drives Ca2+ transport and the A domain rotational motion in the E1P-ADP-2Ca2+ to E2P transition. The dramatic spontaneous decrease in the CC tilting angle of the E2 state drives the restart of the transport cycle.

Targeted mutagenesis of negatively charged amino acids outlining the substrate translocation path within the human organic cation transporter 3.

Recently published cryo-EM structures of human organic cation transporters of the SLC22 family revealed seven, sequentially arranged glutamic and aspartic acid residues, which may be relevant for interactions with positively charged substrates. We analyzed the functional consequences of removing those negative charges by creating D155N, E232Q, D382N, E390Q, E451Q, E459Q, and D478N mutants of OCT3. E232Q, E459Q, and D478N resulted in a lack of localization in the outer cell membrane and no relevant uptake activity. However, D155N and E451Q showed a substrate-specific loss of transport activity, whereas E390Q had no remaining activity despite correct membrane localization. In contrast, D382N showed almost wild-type-like uptake. D155 is located at the entrance to the substrate binding pocket and could, therefore be involved in guiding cationic substrates towards the inside of the binding pocket. For E390, we confirm its critical function for transporter function as it was recently shown for the corresponding position in OCT1. Interestingly, E451 seems to be located at the bottom of the binding pocket in the outward-open confirmation of the transporter. Substrate-specific loss of transport activity of the E451Q variant suggests an essential role in the transport cycle of specific substances as part of an opportunistic binding site. In general, our study highlights the impact of the cryo-EM structures in guiding mutagenesis studies to understand the molecular level of transporter-ligand interactions, and it also confirms the importance of testing multiple substrates in mutagenesis studies of polyspecific OCTs.

A Conserved Intramolecular Ion-Pair Plays a Critical but Divergent Role in Regulation of Dimerization and Transport Function among the Monoamine Transporters.

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters. The disruption of the ion-pair interactions by mutations induced a significant spontaneous cross-linking of a cysteine mutant of SERT and an increase in cell surface expression but with an impaired specific transport activity. On the other hand, similar mutations of the corresponding ion-pair residues in both DAT and NET resulted in an opposite effect on their oxidation-induced dimerization, cell surface expression, and transport function. Reversible biotinylation experiments indicated that the ion-pair mutations slowed down the internalization of SERT but stimulated the internalization of DAT. In addition, cysteine accessibility measurements for monitoring SERT conformational changes indicated that substitution of the ion-pair residues resulted in profound effects on the rate constants for cysteine modification in both the extracellular and cytoplasmatic substrate permeation pathways. Furthermore, molecular dynamics simulations showed that the ion-pair mutations increased the interfacial interactions in a SERT dimer but decreased it in a DAT dimer. Taken together, we propose that the transport function is modulated by the equilibrium between monomers and dimers on the cell surface, which is regulated by a potential compensatory mechanism but with different molecular solutions among the monoamine transporters. The present study provided new insights into the structural elements regulating the transport function of the monoamine transporters through their dimerization.

Characterization of herpetrione amorphous nanoparticles stabilized by hydroxypropylmethyl cellulose and its absorption mechanism in vitro.

Herpetrione(HPE) is an effective compound that has been used in the treatment of liver diseases. To improve its dissolution and absorption, herpetrione nanosuspensions was prepared. Nanosuspensions were proved to achieve intact absorption in vivo. However, the transport mechanisms are not fully understood, especially lack of direct evidence of translocation of particulates. In this study, an environment-responsive dye, P4, was loaded into herpetrione amorphous nanoparticles (HPE-ANPs) to elucidate the absorption and transport mechanism of the nanoparticles. And the amount of HPE and nanoparticles in the samples were quantified using HPLC/LC-MS/MS and IVIS with the model of Caco-2 and Caco-2/HT29-MTX. Results demonstrated that HPE is mainly taken up by passive diffusion in the form of free drugs, while HPE-ANPs are internalized by an energy dependent active transport pathway or intracellular endocytosis. It is speculated that HPE-ANPs may change the original entry pathway of drug molecules. Furthermore, the presence of mucus layer and the use of HPMC E15 may contribute to drug absorption to some extent. Transcellular transport study indicates that HPE-ANPs has a poor absorption. In conclusion, the differences in the absorption behavior trends of HPE-ANPs are caused by the difference in particle properties and the form of existence of the drug.

Soil type regulates the divergent loss characteristics of sediment associated carbon and nitrogen in different size classes during rainfall erosion on cultivated lands.

Sediment associated carbon and nitrogen loss under rainfall, an important cause of soil quality degradation and water eutrophication, strongly depends on the intrinsic properties of original soil types. Relative to total loss, the transport behaviors of organic carbon and nitrogen among sediment size classes and response to soil types remain poorly understood. The concentrations of organic carbon (OC) and total nitrogen (TN) in different sediment size classes (>1, 0.25-1, 0.10-0.25, and <0.10 mm) and their contributions to total sediment load during rainfall erosion were determined under field plot rainfall simulation (at 90 mm h-1) on three contrasting soil types (Luvisol, Alisol and Ferralsol) with increased aggregate stability. During rainfall erosion, the concentrations of OC and TN in total and different sized sediments decreased first and then reached a steady state. The variability of OC and TN concentrations (coefficient of variations in 4.2-53.1% and 6.6-41.9%) among sediment size classes decreased from Luvisol to Ferralsol. Compared to original soils, sediments exhibited larger C/N ratios for Luvisol, and smaller values for Alisol, indicating the more selective transport of labile organic matter for weaker aggregated soils. Among sediment size classes, fine particles (<0.10 mm) accounted 69-88% of total OC and TN losses for Luvisol, and decreased to 30-39% for Ferralsol; and the main transport mechanisms of sediment associated OC and TN shifting from suspension-saltation (<0.10 mm) to rolling (>0.25 mm) with increased aggregate stability. Among original soil properties, inorganic cementing agents (including amorphous iron oxides and clay minerals) showed closer relationships with sediment OC and TN losses (|r| = 0.61-0.89, p < 0.001) than organic matter properties (|r| = 0.55-0.87, p < 0.001), further implying the important role of soil aggregate stability across soil types. This study provides an in-depth understanding on soil carbon and nitrogen losses and their divergent characteristics among soil types deserves consideration in the development of erosion model and land management in agricultural systems.

Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter.

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 Å resolution (extending to 2.2 Å at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 Å resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the 'elevator-with-an-operator' mechanism of TRAP transporters.

Spatial distribution characteristics of perfluoroalkyl substances in bulk and grain size fractionated sediments in Shenzhen Bay.

Understanding Perfluoroalkyl substances (PFASs) spatial distribution in natural environments is crucial due to their environmental persistence and potential bioaccumulation. However, limited research has investigated PFASs spatial distribution at a high resolution, especially in the Guangdong-Hong Kong-Macao Greater Bay Area. Here, we examined the composition and concentration of PFASs in 36 bulk surface sediments and grain-size fractionated sediments from 9 representative sites to determine the spatial distribution characteristics in Shenzhen Bay. We found that ΣPFASs decreased gradually from nearshore area to offshore area (0.680 and 0.297 ng g-1 dw, respectively). Furthermore, PFASs are easily adsorbed on fine-grained sediments, likely due to their chain length and hydrophobicity. We argue that the lateral movement of sediments may transport fine-grained sediments associated with ΣPFASs out of the bay, resulting in the spatial difference in ΣPFASs in Shenzhen Bay. Our findings provide important insights into explore the mechanisms associated with preservation and transport of PFASs.

Carboxymethyl cellulose and carboxymethyl chitosan-based composite nanogel as a stable delivery vehicle for oyster peptides: Characterization, absorption and transport mechanism.

An oyster peptide (OPs)-loaded composite nanogel based on carboxymethyl cellulose and carboxymethyl chitosan (CMC@CMCS@OPs) was prepared, and the characterization, absorption and transport mechanism were further investigated. CMC@CMCS@OPs, a dense spherical microstructure with a diameter of ∼64 nm, which enhanced the thermal and digestive stabilities of individual OPs and improved its retention rate of hypoglycemic activity in vitro. The swelling response and in-vitro release profiles showed that CMC@CMCS@OPs could help OPs achieve targeted and controlled release in the intestine. In addition, CMC@CMCS@OPs had no cytotoxicity on Caco-2 cells, and its apparent permeability coefficients increased 4.70-7.45 times compared with OPs, with the absorption rate increased by 129.38 %. Moreover, the transcytosis of CMC@CMCS@OPs nanogel occurred primarily through the macropinocytosis pathway, endocytosis pathway and intestinal efflux transporter-mediated efflux. Altogether, these results suggested that CMC@CMCS@OPs nanogel could be as an effective OPs delivery device for enhancing its stability and absorption.

Molecular Dynamics Simulations of Supramolecular Polymers within Nanoconfinements for Enhanced Oil Recovery.

Supramolecular polymers offer promising potential for enhanced oil recovery (EOR) advancing techniques. Current instrumental analyses face limitations in capturing instantaneous intracomplex motions due to temporal and spatial constraints. The molecular mechanism of supramolecular polymer transport behavior within nanoconfinement is not yet fully understood. Therefore, the self-assembly mechanism of ß-cyclodextrin (ß-CD) and adamantane (ADA)-modified supramolecular polymers (p-AA-ß-CD-ADA) was delved into in this work. Further exploration focuses on the translocation dynamics of p-AA-ß-CD-ADA within nanoconfinement under external driving forces. Results suggest that ß-CD and ADA in p-AA-ß-CD-ADA were assembled into nodes in the form of a host and a guest, combining with a "node-rebar-cement" interaction model encapsulating the formation mechanism of these supramolecular polymers. The heightened density of the hydrate layers at the nanoscale pore throats acts as a constraining factor, resulting in restricted mobility and altered dynamics of the supramolecular polymers. During passage through nanopore throats, host-guest molecules within the supramolecular polymer experience noncovalent dissociation. Notably, these supramolecular polymers exhibit remarkable self-healing capabilities, reinstating their assembly state upon traversing pore throats. This work provides a molecular-level comprehension of the potential utility of supramolecular polymers in EOR processes, offering valuable information for the molecular design of polymers employed for EOR in low-permeability reservoirs.

Efficiency, Kinetics and Mechanism of 4-Nitroaniline Removal from Aqueous Solutions by Emulsion Liquid Membranes Using Type 1 Facilitated Transport.

4-Nitroaniline (4NA) is a common organic pollutant that is released into the environment during the manufacture and processing of a wide variety of industrial products. This article describes the use of an emulsion liquid membrane process to remove 4NA from aqueous solutions using a type 1 facilitated transport mechanism. Optimization of the removal process was carried out by analyzing the efficiency of 4NA removal from the feed phase and the initial apparent feed/membrane fluxes and permeabilities under different experimental conditions. The kinetics of the removal process was analyzed using a simplified mass transfer model involving an empirical mass transfer coefficient calculated from experimental data, assuming that the concentrations of 4NA in the external aqueous phase and in the internal w/o emulsion are uniform. The results show that there is a very good fit between the experimental and model data and that the variation in the values of the overall mass transfer coefficients with the experimental conditions coincides with that of the removal efficiency mentioned above. The transport mechanism was studied by identifying the rate-controlling step of the removal process, using models described for adsorption processes, due to the strong parallelism between the transport mechanisms in adsorption and emulsion liquid membrane processes.

SLC26 Anion Transporters.

Solute carrier family 26 (SLC26) is a family of functionally diverse anion transporters found in all kingdoms of life. Anions transported by SLC26 proteins include chloride, bicarbonate, and sulfate, but also small organic dicarboxylates such as fumarate and oxalate. The human genome encodes ten functional homologs, several of which are causally associated with severe human diseases, highlighting their physiological importance. Here, we review novel insights into the structure and function of SLC26 proteins and summarize the physiological relevance of human members.

Solid-State Electrolytes and Electrode/Electrolyte Interfaces in Rechargeable Batteries.

Solid-state batteries (SSBs) are considered to be one of the most promising candidates for next-generation energy storage systems due to the high safety, high energy density and wide operating temperature range of solid-state electrolytes (SSEs) they use. Unfortunately, the practical application of SSEs has rarely been successful, which is largely attributed to the low chemical stability and ionic conductivity, ineluctable solid-solid interface issues including limited ion transport channels, high energy barriers, and poor interface contact. A comprehensive understanding of ion transport mechanisms of various SSEs, interactions between fillers and polymer matrixes and the role of the interface in SSBs are indispensable for rational design and performance optimization of novel electrolytes. The categories, research advances and ion transport mechanism of inorganic glass/ceramic electrolytes, polymer-based electrolytes and corresponding composite electrolytes are detailly summarized and discussed. Moreover, interface contact and compatibility between electrolyte and cathode/anode are also briefly discussed. Furthermore, the electrochemical characterization methods of SSEs used in different types of SSBs are also introduced. On this basis, the principles and prospects of novel SSEs and interface design are curtly proposed according to the development requirements of SSBs. Moreover, the advanced characterizations for real-time monitoring of interface changes are also brought forward to promote the development of SSBs.

Physics, Structures, and Applications of Fluorite-Structured Ferroelectric Tunnel Junctions.

The interest in ferroelectric tunnel junctions (FTJ) has been revitalized by the discovery of ferroelectricity in fluorite-structured oxides such as HfO2 and ZrO2 . In terms of thickness scaling, CMOS compatibility, and 3D integration, these fluorite-structured FTJs provide a number of benefits over conventional perovskite-based FTJs. Here, recent developments involving all FTJ devices with fluorite structures are examined. The transport mechanism of fluorite-structured FTJs is explored and contrasted with perovskite-based FTJs and other 2-terminal resistive switching devices starting with the operation principle and essential parameters of the tunneling electroresistance effect. The applications of FTJs, such as neuromorphic devices, logic-in-memory, and physically unclonable function, are then discussed, along with several structural approaches to fluorite-structure FTJs. Finally, the materials and device integration difficulties related to fluorite-structure FTJ devices are reviewed. The purpose of this review is to outline the theories, physics, fabrication processes, applications, and current difficulties associated with fluorite-structure FTJs while also describing potential future possibilities for optimization.

TRAPs: the 'elevator-with-an-operator' mechanism.

Tripartite ATP-independent periplasmic (TRAP) transporters are nutrient-uptake systems found in bacteria and archaea. These evolutionary divergent transporter systems couple a substrate-binding protein (SBP) to an elevator-type secondary transporter, which is a first-of-its-kind mechanism of transport. Here, we highlight breakthrough TRAP transporter structures and recent functional data that probe the mechanism of transport. Furthermore, we discuss recent structural and biophysical studies of the ion transporter superfamily (ITS) members and highlight mechanistic principles that are relevant for further exploration of the TRAP transporter system.

Photo-Thermal Mediated Li-ion Transport for Solid-State Lithium Metal Batteries.

The development of lithium-based solid-state batteries (SSBs) has to date been hindered by the limited ionic conductivity of solid polymer electrolytes (SPEs), where nonsolvated Li-ions are difficult to migrate in a polymer framework at room temperature. Despite the improved cationic migration by traditional heating systems, they are far from practical applications of SSBs. Here, an innovative strategy of light-mediated energy conversion is reported to build photothermal-based SPEs (PT-SPEs). The results suggest that the nanostructured photothermal materials acting as a powerful light-to-heat converter enable heating within a submicron space, leading to a decreased Li+ migration barrier and a stronger solid electrolyte interface. Via in situ X-ray diffraction analysis and molecular dynamics simulation, it is shown that the generated heating effectively triggers the structural transition of SPEs from a highly crystalline to an amorphous state, that helps mediate lithium-ion transport. Using the assembled SSBs for exemplification, PT-SPEs function as efficient ion-transport media, providing outstanding capacity retention (96% after 150 cycles) and a stable charge/discharge capacity (140 mA g-1 at 1.0 C). Overall, the work provides a comprehensive picture of the Li-ion transport in solid polymer electrolytes and suggests that free volume may be critical to achieving high-performance solid-state batteries.

Food-Derived Peptides: Beneficial CNS Effects and Cross-BBB Transmission Strategies.

Food-derived peptides, as dietary supplements, have significant effects on promoting brain health and relieving central nervous system (CNS) diseases. However, the blood-brain barrier (BBB) greatly limits their in-brain bioavailability. Thus, overcoming the BBB to target the CNS is a major challenge for bioactive peptides in the prevention and treatment of CNS diseases. This review discusses improvement in the neuroprotective function of food-derived active peptides in CNS diseases, as well as the source of BBB penetrating peptides (BBB-shuttles) and the mechanism of transmembrane transport. Notably, this review also discusses various peptide modification methods to overcome the low permeability and stability of the BBB. Lipification, glycosylation, introduction of disulfide bonds, and cyclization are effective strategies for improving the penetration efficiency of peptides through the BBB. This review provides a new prospective for improving their neuroprotective function and developing treatments to delay or even prevent CNS diseases.