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Copyright of Petroleum Refinery Engineering is the property of Petroleum Refinery Engineering Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the 21st century, research on extracellular vesicles (EVs) has made remarkable advancements. Recently, researchers have uncovered the exceptional biological features of EVs, highlighting their prospective use as therapeutic targets, biomarkers, innovative drug delivery systems, and standalone therapeutic agents. Currently, mesenchymal stem cells stand out as the most potent source of EVs for clinical applications in tissue engineering and regenerative medicine. Owing to their accessibility and capability of undergoing numerous differentiation inductions, dental stem cell-derived EVs (DSC-EVs) offer distinct advantages in the field of tissue regeneration. Nonetheless, it is essential to note that unmodified EVs are currently unsuitable for use in the majority of clinical therapeutic scenarios. Considering the high feasibility of engineering EVs, it is imperative to modify these EVs to facilitate the swift translation of theoretical knowledge into clinical practice. The review succinctly presents the known biotherapeutic effects of odontogenic EVs and the underlying mechanisms. Subsequently, the current state of functional cargo loading for engineered EVs is critically discussed. For enhancing EV targeting and in vivo circulation time, the review highlights cutting-edge engineering solutions that may help overcome key obstacles in the clinical application of EV therapeutics. By presenting innovative concepts and strategies, this review aims to pave the way for the adaptation of DSC-EVs in regenerative medicine within clinical settings.

The present investigation focuses on the impact of jet nozzle orientation on mixing time in a cylindrical tank. The aim is to identify nozzle positions that improve mixing performance and to elucidate the governing parameters that influence it. A water tank was employed for the experiment. The vertical inclination angle (α) and the horizontal inclination angle (β) of the jet nozzle determined the nozzle positions. Mixing time was determined using an inert tracer and spectrophotometry measurements. The findings show that the mixing time is significantly influenced by the position of the jet nozzle position. The accuracy of existing jet turbulence and the circulation models for the prediction of mixing time was evaluated for the different nozzle positions. Our results indicate that both models provide accurate predictions for the conventional centrally aligned (β = 0°), upward-pointing jet nozzle positions only (α > 0). For the other nozzle positions where β > 0° and at varying α, the data follow the same trends as the jet turbulence and circulation models; however, the proportionality constants vary. Shorter mixing times can be attributed principally to longer jet path lengths and therefore higher fluid entrainment and circulation as well as higher dissipation rates per jet length squared. However, it is suspected that the three-dimensional nature of the flow pattern generated in the tank also plays a non-negligible role since mixing is hindered when the nozzle points more towards the tank wall. [ABSTRACT FROM AUTHOR]

Kidney diseases are a serious health issue worldwide, and novel therapeutics are urgently needed. Extracellular vesicles (EVs) have emerged as potent drug delivery systems (DDSs), but their therapeutic potential is limited by short circulation times and insufficient renal retention. Here, we report that endogenous ligand (albumin, ALB) binding is an efficient modification strategy to improve the therapeutic potency of EV-based DDSs for kidney diseases. Surface albumin-binding peptide (ABP)-displayed EVs (ABP-EVs) were produced by transfecting parent cells with the ABP-Lamp2b fusion plasmid. Compared with unmodified EVs (NC-EVs), ABP-EVs showed increased binding to ALB in vitro and elevated circulation time and multiple organ retention in vivo after systemic (iv) injection. Moreover, ABP-EVs had higher renal retention than NC-EVs in mice with acute kidney injury through a complex mechanism involving microvascular injury and megalin-mediated endocytosis. As a result, delivery of small molecule drugs (e.g. , curcumin) or proteins (e.g. , hepatocyte growth factor) by ABP-EVs had superior therapeutic (e.g. , anti-apoptotic, antioxidant, anti-inflammatory) effects in vitro and in vivo. This study highlights that ABP-EVs are versatile DDSs for kidney diseases and provides insights into the new strategies of engineering EVs for drug delivery. [Display omitted] • Surface albumin-binding peptide-displayed extracellular vesicles (ABP-EVs) can bind to endogenous ALB. • ABP-EVs showed higher levels of circulation time and multiple organ retention in vivo than native unmodified EVs. • ABP-EVs enhanced the therapeutic index of delivered drugs in mice with kidney injury. • Endogenous ligand binding may be an efficient strategy to improve the renoprotective potency of EV-based therapies. [ABSTRACT FROM AUTHOR]

The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time. For most drugs, sufficient in vivo circulation time is the basis of high bioavailability. Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system, to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect. The physical and chemical properties of drug carriers, such as size, shape, surface charge and surface modification, would affect their in vivo circulation time, metabolic behavior and biodistribution. The final circulation time of carriers is determined by the balance between macrophage recognitions, blood vessel penetration and urine excretion. Therefore, when designing the drug delivery system, we should pay much attention to the properties of drug carriers to get enough in vivo circulation time to arrive at target site eventually. This article mainly reviews the effect of carrier size, size, surface charge and surface properties on its circulation time in vivo, and discusses the mechanism of these properties affecting circulation time. This review has reference significance for the research of long-circulation drug delivery system.

Abstract Extracellular vesicles (EVs) have shown promise as potential therapeutics for the treatment of various diseases. However, their rapid clearance after administration could be a limitation in certain therapeutic settings. To solve this, an engineering strategy is employed to decorate albumin onto the surface of the EVs through surface display of albumin binding domains (ABDs). ABDs were either included in the extracellular loops of select EV‐enriched tetraspanins (CD63, CD9 and CD81) or directly fused to the extracellular terminal of single transmembrane EV‐sorting domains, such as Lamp2B. These engineered EVs exert robust binding capacity to human serum albumins (HSA) in vitro and mouse serum albumins (MSA) after injection in mice. By binding to MSA, circulating time of EVs dramatically increases after different routes of injection in different strains of mice. Moreover, these engineered EVs show considerable lymph node (LN) and solid tumour accumulation, which can be utilized when using EVs for immunomodulation, cancer‐ and/or immunotherapy. The increased circulation time of EVs may also be important when combined with tissue‐specific targeting ligands and could provide significant benefit for their therapeutic use in a variety of disease indications.

Extracellular vesicles (EVs) have shown promise as potential therapeutics for the treatment of various diseases. However, their rapid clearance after administration could be a limitation in certain therapeutic settings. To solve this, an engineering strategy is employed to decorate albumin onto the surface of the EVs through surface display of albumin binding domains (ABDs). ABDs were either included in the extracellular loops of select EV‐enriched tetraspanins (CD63, CD9 and CD81) or directly fused to the extracellular terminal of single transmembrane EV‐sorting domains, such as Lamp2B. These engineered EVs exert robust binding capacity to human serum albumins (HSA) in vitro and mouse serum albumins (MSA) after injection in mice. By binding to MSA, circulating time of EVs dramatically increases after different routes of injection in different strains of mice. Moreover, these engineered EVs show considerable lymph node (LN) and solid tumour accumulation, which can be utilized when using EVs for immunomodulation, cancer‐ and/or immunotherapy. The increased circulation time of EVs may also be important when combined with tissue‐specific targeting ligands and could provide significant benefit for their therapeutic use in a variety of disease indications. [ABSTRACT FROM AUTHOR]

Self‐assembling filomicelles (FMs) are of great interest to nanomedicine due to their structural flexibility, extensive systemic circulation time, and amenability to unique “cylinder‐to‐sphere” morphological transitions. However, current fabrication techniques for preparing FMs are highly variable and difficult to scale. Herein, it is demonstrated that tetrablock copolymers composed of poly(ethylene glycol)‐b‐poly(propylene sulfide) (PEG‐b‐PPS) diblocks linked by a pi‐stacking perylene bisimide (PBI) moiety permit rapid, scalable, and facile assembly of FMs via the flash nanoprecipitation (FNP) method. Coassembling the tetrablocks and PEG‐b‐PPS diblocks at different molar ratios resulted in mixed PBI‐containing FMs (mPBI‐FM) with tunable length and flexibility. The flexibility of mPBI‐FM can be optimized to decrease uptake by macrophages in vivo, leading to increased circulation time versus (−)PBI‐FM without PBI tetrablocks after intravenous administration in mice. While PEG‐b‐PPS diblocks form FM within a narrow range of hydrophilic weight fractions, incorporation of pi‐stacking PBI groups expanded this range to increase favorability of FM assembly. Furthermore, the aggregation‐dependent fluorescence of PBI shifted during oxidation‐induced “cylinder‐to‐sphere” transitions of mPBI‐FM into micelles, resulting in a distinct emission wavelength for filamentous versus spherical nanostructures. Thus, incorporation of pi‐stacking allows for rapid, scalable assembly of FMs with tunable flexibility and stability for theranostic and nanomedicine applications.

It is well known that the hydrodynamics of dense gas–particle flows depends heavily on inter-particle and particle–wall collisions; however, the subtleties of these interactions are not always fully recognized or appreciated. In this study, the two-fluid model is used to systematically examine the effects of collision parameters, i.e., particle–particle restitution coefficient, particle–wall restitution coefficient, and wall specularity coefficient, on simulations of the hydrodynamics of a pseudo two-dimensional bubbling fluidized bed. The utilization of high-resolution Eulerian simulations facilitates the representation of meso-scale structures without the use of a sub-grid scale model, while qualitatively reflecting the experimental data. To ensure statistically robust results and increase confidence in the simulations, a careful assessment of the time-averaging interval was first undertaken to smooth out the fluctuations that persist even after the bed reaches steady state. A quantitative analysis was then performed to analyze important facets of the flow, including bubble characteristics, particle velocity fields, and granular temperature. The underlying physical formulation was employed to elucidate how collision parameters impact the hydrodynamics of the flow. The notable findings of this study are threefold. First, the specific details of the collisions between particles are shown to significantly influence the bubble characteristics and overall flow pattern. However, the effect of the particle–particle restitution coefficient turns out to be minimal on the bed circulation time except in the limit of particle elastic collisions. It is also found that the elastic collision of particles highly affects the bubble count and unexpectedly changes the role of the wall from a source to a sink of granular temperature. Second, the effect of the particle–wall restitution coefficient is appreciable on the granular temperature while having a minimal effect on the flow hydrodynamics. Third, the effect of the wall specularity coefficient is felt across the bed such that an increase in this parameter increases the bed circulation time. The results of this systematic study enhance the understanding of how collision parameters impact flow characteristics while also providing insight into the selection of their values in simulations. • Rigorous time-averaging suggests an intermittent flow behavior. • Bubble count is mostly unaffected unless inter-particle collisions are elastic. • The wall specularity coefficient can reverse the flow direction in the core region. • The particle–wall restitution coefficient highly affects the granular temperature. [ABSTRACT FROM AUTHOR]

Background: Conventional metrics to evaluate sleep-disordered breathing (SDB) have many limitations, including their inability to identify subclinical markers of cardiovascular (CV) dysfunction.Research Question: Does sleep study-derived circulation time (Ct) predict mortality, independent of CV risks and SDB severity?Study Design and Methods: We derived average lung to finger Ct (LFCt) from sleep studies in older men enrolled in the multicenter Osteoporotic Fractures in Men (MrOS) Sleep study. LFCt was defined as the average time between end of scored respiratory events and nadir oxygen desaturations associated with those events. We calculated the hazard ratio (HRs) for the CV and all-cause mortality by LFCt quartiles, adjusting for the demographic characteristics, body habitus, baseline CV risk, and CV disease (CVD). Additional models included apnea-hypopnea index (AHI), time with oxygen saturation as measured by pulse oximetry (SpO2) < 90% (T90), and hypoxic burden. We also repeated analyses after excluding those with CVD at baseline.Results: A total of 2,631 men (mean ± SD age, 76.4 ± 5.5 years) were included in this study. LFCt median (interquartile range) was 18 (15-22) s. During an average ± SD follow-up of 9.9 ± 3.5 years, 427 men (16%) and 1,205 men (46%) experienced CV death and all-cause death, respectively. In multivariate analysis, men in the fourth quartile of LFCt (22-52 s) had an HR of 1.36 (95% CI, 1.02-1.81) and 1.35 (95% CI, 1.14-1.60) for CV and all-cause mortality, respectively, when compared with men in the first quartile (4-15 s). The results were similar when additionally adjusting for AHI, T90, or hypoxic burden. Results were stronger among men with no history of CVD at baseline.Interpretation: LFCt is associated with both CV and all-cause mortality in older men, independent of baseline CV burden and SDB metrics. LFCt may be a novel physiologic marker for subclinical CVD and adverse outcomes in patients with SDB. [ABSTRACT FROM AUTHOR]

Porous silicon (PSi) nanoparticles are capable of delivering therapeutic payloads providing targeted delivery and sustained release of the payloads. In this work we describe the development and proof-of-concept in vivo evaluation of thermally hydrocarbonized porous silicon (PSi) nanoparticles that are implanted with radioactive 155Tb atoms and coated with red blood cell (RBC) membrane (155Tb-THCPSi). The developed nanocomposites can be utilized as an intravenous delivery platform for theranostic radionuclides. THCPSi thin films were implanted with 155Dy ions that decay to 155Tb at the ISOLDE radioactive ion-beam (RIB) facility at CERN. The films were processed to nanoparticles by ball-milling and sonication, and subsequently coated with either a solid lipid and RBC membrane or solely with RBC membrane. The nanocomposites were evaluated in vitro for stability and in vivo for circulation half-life and ex vivo for biodistribution in Balb/c mice. Nanoporous THCPSi films were successfully implanted with 155Tb and processed to coated nanoparticles. The in vitro stability of the particles in plasma and buffer solutions was not significantly different between the particle types, and therefore the RBC membrane coated particles with less laborious processing method were chosen for the biological evaluation. The RBC membrane coating enhanced significantly the blood half-life compared to bare THCPSi particles. In the ex vivo biodistribution study a pronounced accumulation to the spleen was found, with lower uptake in the liver and a minor uptake in the lung, gall bladder and bone marrow. We have demonstrated, using 155Tb RIB-implanted PSi nanoparticles coated with mouse RBC membranes, the feasibility of using such a theranostic nanosystem for the delivery of RIB based radionuclides with prolonged circulation time. For the first time, the RIB implantation technique has been utilized to produce PSi nanoparticle with a surface modified for better persistence in circulation. When optimized, these particles could be used in targeted radionuclide therapy with a combination of chemotherapeutic payload within the PSi structure. [ABSTRACT FROM AUTHOR]

Drug carriers based on polyelectrolyte microcapsules remotely controlled with an external magnetic field are a promising drug delivery system. However, the influence of capsule parameters on microcapsules’ behavior in vivo is still ambiguous and requires additional study. Here, we discuss how the processes occurring in the blood flow influence the circulation time of magnetic polyelectrolyte microcapsules in mouse blood after injection into the blood circulatory system and their interaction with different blood components, such as WBCs and RBCs. The investigation of microcapsules ranging in diameter 1–5.5 μm allowed us to reveal the dynamics of their filtration by vital organs, cytotoxicity, and hemotoxicity, which is dependent on their size, alongside the efficiency of their interaction with the magnetic field. Our results show that small capsules have a long circulation time and do not affect blood cells. In contrast, the injection of large 5.5 μm microcapsules leads to fast filtration from the blood flow, induces the inhibition of macrophage cell line proliferation after 48 h, and causes an increase in hemolysis, depending on the carrier concentration. The obtained results reveal the possible directions of fine-tuning microcapsule parameters, maximizing capsule payload without the side effects for the blood flow or the blood cells.

To develop and test a model predicting 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) standardized uptake value (SUV) changes over time in the aorta and the superior vena cava (SVC). Maximum aortic SUV and mean SVC SUV were determined at two time points (T1 and T2) in the ascending (ASC), descending (DSC), abdominal (ABD) aorta, aortic arch (ARC) and SVC of patients who have undergone [18F]FDG PET/CT for clinical purposes. For SUV prediction at T2, linear and non-linear models of SUV difference for a given time change were developed in a derivation group. The results were tested in an independent validation group, whilst model reproducibility was tested in patients of the validation group who have undergone a second clinically indicated scan. Applying the linear model in the derivation group, there were no statistically significant differences in measurements obtained in the examined segments: mean differences ranged from 0 ± 0.10 in SVC to 0.01 ± 0.13 in ARC between measured and predicted SUV. In contrast, in the non-linear model, there were statistically significant differences in measurements, except in ARC, with mean differences ranging from 0.04 ± 0.14 in ARC to 0.28 ± 0.13 in ABD. In the validation group using the linear model, there were no statistically significant differences, with mean differences ranging from - 0.01 ± 0.08 in ASC to - 0.03 ± 0.11 in ABD. Regarding reproducibility, mean differences were no statistically significant, ranging from 0.004 ± 0.06 in ASC to - 0.02 ± 0.16 in ABD. We have developed a linear model allowing accurate and reproducible prediction of SUV changes over time in the aorta and SVC. [ABSTRACT FROM AUTHOR]

Copyright of China Petroleum Machinery is the property of China Petroleum Machinery Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The properties of modified biomaterial are gaining more and more importance in drug delivery systems. Sialic acid (SA) and polysialic acid (PSA) serve as endogenous substances, which are non-immunogenic and biodegradable. At the same time, SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain; PSA modification can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood, thus achieving active targeting effect. These properties offer a variety of opportunities for applications in drug delivery systems. This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs, proteins and carriers in drug delivery systems.

The use of nanoparticles as tumor-targeting agents is steadily increasing, and the influence of nanoparticle characteristics such as size and stealthiness have been established for a large number of nanocarrier systems. However, not much is known about the impact of tumor presence on nanocarrier circulation times. This paper reports on the influence of tumor presence on the in vivo circulation time and biodistribution of polybutadiene-polyethylene oxide (PBd-PEO) polymersomes. For this purpose, polymersomes were loaded with the gamma-emitter 111In and administered intravenously, followed by timed ex vivo biodistribution. A large reduction in circulation time was observed for tumor-bearing mice, with a circulation half-life of merely 5 min (R2 = 0.98) vs 117 min (R2 = 0.95) in healthy mice. To determine whether the rapid polymersome clearance observed in tumor-bearing mice was mediated by macrophages, chlodronate liposomes were administered to both healthy and tumor-bearing mice prior to the intravenous injection of radiolabeled polymersomes to deplete their macrophages. Pretreatment with chlodronate liposomes depleted macrophages in the spleen and liver and restored the circulation time of the polymersomes with no significant difference in circulation time between healthy mice and tumor-bearing mice pretreated with clodronate liposomes (15.2 ± 1.2% ID/g and 13.6 ± 2.7% ID/g, respectively, at 4 h p.i. with p = 0.3). This indicates that activation of macrophages due to tumor presence indeed affected polymersome clearance rate. Thus, next to particle design, the presence of a tumor can also greatly impact circulation times and should be taken into account when designing studies to evaluate the distribution of polymersomes.

Durability is a very important property of currency and currency paper because currency is circulated in the public for a very long time. The effect of circulation time on the physical properties of currency was investigated. In addition, a crumpling treatment procedure was adopted to simulate the circulation of currency in public. The air permeance of currency that was subjected to eight rounds of crumpling treatment was compared with that of actual circulated currency. As the circulation time increased, the basis weight, thickness, air permeance, and b* value increased. On the other hand, the stiffness and the L* value decreased as the circulation time increased. Regarding the air permeance, the slope of the plot was greater than the slopes of other physical properties measured. Air permeance of the samples after the crumpling treatment was greater than that of the circulated currency, which indicated that the crumpling process resulted in more severe changes in air permeance than the crumpling that occurs during the actual circulation of currency. [ABSTRACT FROM AUTHOR]

Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu (DSS), palmitoyl Danshensu (PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL −1 , its solubility in FaSSIF and FeSSIF reached 4.68 and 9.08 mg·mL −1 , respectively. Octanol-water partition coefficient (log P ) was increased from −2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t 1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. C max was 1.67 ± 0.11 μg·mL −1 for PDSS and 0.81 ± 0.06 μg·mL −1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug. [ABSTRACT FROM AUTHOR]

Metastatic cascade is a multi-stage process that starts with separation of a cancer cell from the primary tumor and ends with the emergence of a detectable metastasis. In the process the initiator cancer cell enters the circulatory system (intravasates), flows with the blood, and exits the circulation (extravasates) into an organ or tissue. The time period between intravasation and extravasation constitutes the circulation stage of the metastatic cascade. This stage is unique in that it lends itself naturally to various non-invasive observations and measurements in an individual cancer patient. This creates an opportunity for gaining insight into metastasis, its mathematical modeling, and designing diagnostic/prognostic tools and new cancer therapies. Although mechanisms of intravasation, survival and extravasation of circulating tumor cells (CTCs) are very complex and largely unknown, mathematical modeling of the circulation stage of the metastatic cascade is facilitated by two inter-related factors: a relative simplicity of the circulatory network and the cyclic nature of blood flow. The article presents a single-subject stochastic model of CTC dynamics that leads to simple formulas, applicable to any homogeneous CTC population, for organ-specific extravasation probabilities, the distribution and expected value of the number, X , of circulation cycles completed by a CTC prior to extravasation, and the average circulation time. In particular, we found that the distribution of random variable X is geometric G (x) , where parameter x is measurable, at least in principle, in an individual subject. We also discuss implications of our results for cancer research and treatment. • A single-patient mathematical model for the dynamics of bloodborne CTCs was designed. • Extravasation probabilities for CTCs bound for a given organ were computed. • Distribution of the number of circulation cycles prior to CTC extravasation was identified. • Expected CTC circulation time preceding CTC extravasation was computed. • Parameters built into these quantities for an individual subject are measurable. [ABSTRACT FROM AUTHOR]