Analysis on efficacy of magnetic resonance lymphangiography using INV-001 in healthy beagle dogs.

We aimed to conduct a proof-of-concept study of INV-001 in visualizing lymphatic vessels and nodes without venous contamination and to determine the optimal dose condition of INV-001 for magnetic resonance lymphangiography (MRL) in healthy beagles. MRL was performed using a 3.0-Tesla (T) whole body clinical magnetic resonance imaging (MRI) scanner. A dose-finding study of INV-001 for MRL in beagles (N = 6) was carried out according to an adaptive optimal dose finding design. For the reproducibility study (N = 6), MRL was conducted at selected INV-001 doses (0.056 and 0.112 mg Fe/kg) with a 15 mM concentration. Additionally, an excretion study (N = 3) of INV-001 was conducted by analyzing T1, T2, and T2* maps of the liver and kidney 48 h post-administration. INV-001 administration at doses of 0.056 and 0.112 mg Fe/kg (concentration: 15 mM) consistently demonstrated the visualization of contrast-enhanced lymphatic vessels and nodes without venous contamination in the beagles. The contrast enhancement effect was highest at 30 min after INV-001 administration, then gradually decreasing. No toxicity-related issues were identified during the study. After 48 h, the T1, T2, and T2* values in the liver and both kidneys were found to be comparable to the pre-administration values, indicating thorough INV-001 excretion. The optimal dosing conditions of INV-001 for MRL for contrast-enhanced visualization of lymphatic vessels and nodes exclusively with no venous contamination in beagles was determined to be 0.056 mg Fe/kg with a 15 mM concentration.

Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography.

PURPOSE: Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues. The study further explores the optimal dosage, including both injection volume and concentration, required to achieve successful visualization of the popliteal lymph nodes and surrounding lymphatic vessels. PROCEDURES: All animals utilized in this study were male Sprague-Dawley (SD) rats weighing between 250 and 300 g. The contrast agents prepared were injected intradermally in the fourth phalanx of both hind limbs using a 30-gauge syringe in SD rats. MRL was performed every 16 min on a coronal 3D time-of-flight sequence with saturation bands using a 9.4-T animal machine. RESULTS: Contrary to Gd-DOTA, which exhibited venous contamination in most animals irrespective of injection dosages and conditions, INV-001 showed no venous contamination. For Gd-DOTA, the popliteal lymph nodes and lymphatic vessels reached peak enhancement 16 min after injection from the injection site and then rapidly washed out. However, with INV-001, they reached peak enhancement between 16 and 32 min after injection, with prolonged visualization of the popliteal lymph node and lymphatic vessels. INV-001 at 0.45 µmol (15 mM, 30 µL) and 0.75 µmol (15 mM, 50 µL) achieved high scores for qualitative image analysis, providing good visualization of the popliteal lymph nodes and lymphatic vessels without issues of venous contamination, interstitial space enhancement, or lymph node enlargement. CONCLUSION: In MRL, INV-001, a novel T1 contrast agent based on iron, enables prolonged enhancement of popliteal lymph nodes and lymphatic vessels without venous contamination.

Ultrasmall Mn-doped iron oxide nanoparticles with dual hepatobiliary and renal clearances for T1 MR liver imaging.

Although magnetic nanoparticles demonstrate significant potential as magnetic resonance imaging (MRI) contrast agents, their negative contrasts, liver accumulation, and limited excretion hinder their application. Herein, we developed ultrasmall Mn-doped iron oxide nanoparticles (UMIOs) with distinct advantages as T1 MRI contrast agents. Exceptionally small particle sizes (ca. 2 nm) and magnetization values (5 emu gMn+Fe-1) of UMIOs provided optimal T1 contrast effects with an ideally low r2/r1 value of ∼1. Furthermore, the use of Mn as a dopant facilitated hepatocyte uptake of the particles, allowing liver imaging. In animal studies, UMIOs exhibited significantly enhanced contrasts for sequential T1 imaging of blood vessels and the liver, distinguishing them from conventional magnetic nanoparticles. UMIOs were systematically cleared via dual hepatobiliary and renal excretion pathways, highlighting their safety profile. These characteristics imply substantial potential of UMIOs as T1 contrast agents for the accurate diagnosis of liver diseases.

A Methodological Approach for Motor Selection in Dental Impression Material Dispensers Using Experimental and Image Analysis Techniques.

This study presents a methodology to prevent the overdesign of electric dispensers for dental impression materials by analyzing the necessary load and determining the appropriate pressurization speed and drive motor capacity. We derived an equation to calculate the required torque and rotational speed of the motor based on the extrusion load and the speed of the impression material. A specialized load measurement system was developed to measure the load necessary to extrude the impression material. Through experiments and image processing, we measured the radius of curvature of the trajectory of the impression material and correlated it with the pressurization speed. Techniques such as position coordinate plotting, curve fitting, and circle fitting were employed to determine the pressurization speed that aligns with the manufacturer's recommended curvature radius. These findings led to a substantial decrease in the necessary motor torque and rotational speed compared with the current standards. This research provides a systematic approach to sizing drive motors using extrusion load and pressurization speed, aiming to reduce overdesign, power consumption, and the weight and size of the motor and battery, thereby contributing to the development of more efficient and compact dental impression material dispensers.

PDZ Peptide of the ZO-1 Protein Significantly Increases UTP-Induced MUC8 Anti-Inflammatory Mucin Overproduction in Human Airway Epithelial Cells.

Mucus hyperproduction and hypersecretion are observed often in respiratory diseases. MUC8 is a glycoprotein synthesized by epithelial cells and generally expressed in the respiratory track. However, the physiological mechanism by which extracellular nucleotides induce MUC8 gene expression in human airway epithelial cells is unclear. Here, we show that UTP could induce MUC8 gene expression through P2Y2-PLCß3-Ca2+ activation. Because the full-length cDNA sequence of MUC8 has not been identified, a specific siRNA-MUC8 was designed based on the partial cDNA sequence of MUC8. siRNA-MUC8 significantly increased TNF-α production and decreased IL-1Ra production, suggesting that MUC8 may downregulate UTP/P2Y2-induced airway inflammation. Interestingly, the PDZ peptide of ZO-1 protein strongly abolished UTP-induced TNF-α production and increased IL-1Ra production and MUC8 gene expression. In addition, the PDZ peptide dramatically increased the levels of UTP-induced ZO proteins and TEER (trans-epithelial electrical resistance). These results show that the anti-inflammatory mucin MUC8 may contribute to homeostasis, and the PDZ peptide can be a novel therapeutic candidate for UTP-induced airway inflammation.

The Effect of Boron (B) and Copper (Cu) on the Microstructure and Graphite Morphology of Spheroidal Graphite Cast Iron.

This study examines the impacts of copper and boron in parts per million (ppm) on the microstructure and mechanical properties of spheroidal graphite cast iron (SCI). Boron's inclusion increases the ferrite content whereas copper augments the stability of pearlite. The interaction between the two significantly influences the ferrite content. Differential scanning calorimetry (DSC) analysis indicates that boron alters the enthalpy change of the α + Fe3C → γ conversion and the α → γ conversion. Scanning electron microscope (SEM) analysis confirms the locations of copper and boron. Mechanical property assessments using a universal testing machine show that the inclusion of boron and copper decreases the tensile strength and yield strength of SCI, but simultaneously enhances elongation. Additionally, in SCI production, the utilization of copper-bearing scrap and trace amounts of boron-containing scrap metal, especially in the casting of ferritic nodular cast iron, offers potential for resource recycling. This highlights the importance of resource conservation and recycling in advancing sustainable manufacturing practices. These findings provide critical insights into the effects of boron and copper on SCI's behavior, contributing to the design and development of high-performance SCI materials.

Prediction of Extrusion Machine Stem Fatigue Life Using Structural and Fatigue Analysis.

In this study, the characteristics of the SKD61 material used for the stem of an extruder were analyzed through structural analysis, tensile testing, and fatigue testing. The extruder works by pushing a cylindrical billet into a die with a stem to reduce its cross-sectional area and increase its length, and it is currently used to extrude complex and diverse shapes of products in the field of plastic deformation processes. Finite element analysis was used to determine the maximum stress on the stem, which was found to be 1152 MPa, lower than the yield strength of 1325 MPa obtained from tensile testing. Fatigue testing was conducted using the stress-life (S-N) method, considering the characteristics of the stem, and statistical fatigue testing was employed to create an S-N curve. The predicted minimum fatigue life of the stem at room temperature was 424,998 cycles at the location with the highest stress, and the fatigue life decreased with increasing temperature. Overall, this study provides useful information for predicting the fatigue life of extruder stems and improving their durability.

Complete mitochondrial genome of Aleochara (Aleochara) curtula (Goeze, 1777) (Coleoptera: Staphylinidae).

The mitochondrial genome (mitogenome) of Aleochara (Aleochara) curtula (Goeze, 1777) (Coleoptera: Staphylinidae) is reported. This mitogenome (GenBank accession no. OL675411) is 16,600 bp in size and consists of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNA). Most PCGs use typical mitochondrial stop codon (TAR) except for cox3, which uses a single T residue. The A, G, T, and C nucleotide base composition of the mitogenome is 40.61%, 7.66%, 40.34%, and 11.39%, respectively. The phylogenetic analyses recovered the monophyly of Aleocharinae.

Approximation Model Development and Dynamic Characteristic Analysis Based on Spindle Position of Machining Center.

To evaluate the dynamic characteristics at all positions of the main spindle of a machine tool, an experimental point was selected using a full factorial design, and a vibration test was conducted. Based on the measurement position, the resonant frequency was distributed from approximately 236 to 242 Hz. The approximation model was evaluated based on its resonant frequencies and dynamic stiffness using regression and interpolation methods. The accuracy of the resonant frequency demonstrated by the kriging method was approximately 89%, whereas the highest accuracy of the dynamic stiffness demonstrated by the polynomial regression method was 81%. To further verify the approximation model, its dynamic characteristics were measured and verified at additional experimental points. The maximum errors yielded by the model, in terms of the resonant frequency and dynamic stiffness, were 1.6% and 7.1%, respectively.

Development of markers using microsatellite loci of two rove beetle species, Paederus fuscipes Curtis and Aleochara (Aleochara) curtula Goeze (Coleoptera: Staphylinidae), followed by analyses of genetic diversity and population structure.

BACKGROUND: The family Staphylinidae is the most speciose beetle group in the world. The outbreaks of two staphylinid species, Paederus fuscipes and Aleochara (Aleochara) curtula, were recently reported in South Korea. None of research about molecular markers and genetic diversity have been conducted in these two species. OBJECTIVE: To develop microsatellite markers and analyze the genetic diversity and population structures of two rove beetle species. METHODS: NGS was used to sequence whole genomes of two species, Paederus fuscipes and Aleochara (Aleochara) curtula. Microsatellite loci were selected with flanking primer sequences. Specimens of P. fuscipes and A. curtula were collected from three localities, respectively. Genetic diversity and population structure were analyzed using the newly developed microsatellite markers. RESULTS: The number of alleles ranged 5.727-6.636 (average 6.242) and 2.182-5.364 (average 4.091), expected heterozygosity ranged 0.560-0.582 (average 0.570) and 0.368-0.564 (average 0.498), observed heterozygosity ranged 0.458-0.497 (average 0.472) and 0.418-0.644 (average 0.537) in P. fuscipes and A. curtula, respectively. Population structure indicates that individuals of A. curtula are clustered to groups where they were collected, but those of P. fuscipes are not. CONCLUSION: Population structures of P. fuscipes were shallow. In A. curtula, however, it was apparent that the genetic compositions of the populations are different significantly depending on collection localities.

Pseudo single domain NiZn-γFe2O3colloidal superparamagnetic nanoparticles for MRI-guided hyperthermia application.

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) is highly desirable in cancer treatment because it can allow for diagnosis, therapeutics, and prognosis simultaneously. However, the application of currently developed iron-oxide based superparamagnetic nanoparticles (IOSPNPs) for an MRI-guided MNFH agent is technically limited by the low AC heat induction power at the physiologically tolerable range of AC magnetic field (HAC,safe), and the low transverser2-relaxivity responsible for the insufficient heating of cancers, and the low resolution of contrast imaging, respectively. Here, pseudo single domain colloidal NixZn1-x-γFe2O3(x = 0.6) superparamagnetic nanoparticle (NiZn-γFe2O3PSD-SPNP) physically and theoretically designed at theHAC,safe, specifically by the applied frequency, is proposed for a highly enhanced MRI-guided MNFH agent application. The NiZn-γFe2O3PSD-SPNP showed the superparamagnetic characteristics, significantly enhanced AC heat induction performance (ILP = 6.3 nHm2kg-1), highly improved saturation magnetization (Ms= 97 emu g-1Fe, 3.55 × 105A m-1) andr2-relaxivity (r2 = 396 mM-1s-1) that are desirable for highly efficient MRI-guided MNFH agent applications. According to the analyzed results, the remarkably enhanced effective relaxation time constant and its dependent out-of-phase magnetic susceptibility, as well as the DC/AC magnetic softness optimized by the PSD-SPNP at theHAC,safewere revealed as the main physical reason for the significance. All the fundamentalin vitroandin vivoexperimental results demonstrated that the physically designed NiZn-γFe2O3PSD-SPNP is bio-technically feasible for a highly efficient MRI-guided MNFH agent for future cancer nanomedicine.

Pseudo-single domain colloidal superparamagnetic nanoparticles designed at a physiologically tolerable AC magnetic field for clinically safe hyperthermia.

Magnetic nanofluid hyperthermia (MNFH) with pure superparamagnetic nanoparticles (P-SPNPs) has drawn a huge attraction for cancer treatment modality. However, the low intrinsic loss power (ILP) and attributable degraded-biocompatibility resulting from the use of a heavy dose of P-SPNP agents as well as low heat induction efficiency in biologically safe AC magnetic field (HAC,safe) are challenging for clinical applications. Here, we report an innovatively designed pseudo-single domain-SPNP (PSD-SPNP), which has the same translational advantages as that of conventional P-SPNPs but generates significantly enhanced ILP at HAC,safe. According to the analyzed results, the optimized effective relaxation time, τeff, and magnetic out-of-phase susceptibility, χ'', precisely determined by the particle size at the specific frequency of HAC,safe are the main reasons for the significantly enhanced ILP. Additionally, in vivo MNFH studies with colloidal PSD-SPNPs strongly demonstrated that it can be a promising agent for clinically safe MNFH application with high efficacy.

Reliable evaluation method of heating power of magnetic nanofluids to directly predict the tumor temperature during hyperthermia.

Reliable measurement of heating power of magnetic nanofluids (MNs) to accurately predict the AC heat-induction performance in tumors is highly desirable for clinical magnetic nanofluids hyperthermia (MNFH) application because it can save time for screening the performance of newly developed MNFH agent and minimize the over-use of animals dramatically. Here, a bio-mimicking phantom model, called Pseudo-Tumor Environment System (P-TES), biochemically designed by considering the external and internal critical factors related to the complex biological environments is proposed to provide a highly reliable evaluation method of heating performance of MNs for in-vivo MNFH applications. According to the experimentally analyzed results, the heating power of MNs measured using the P-TES is well accorded with the heating temperature measured in the tumors during in-vivo MNFH. This result strongly demonstrates that the proposed P-TES can be recommended as a standardized measurement method of heating performance of MNs for clinical MNFH application.

The correlation between the STOP-Bang score and oxygen saturation during spinal anesthesia with dexmedetomidine sedation.

BACKGROUND: The STOP-Bang questionnaire is a simple screening tool with high sensitivity for the detection of severe obstructive sleep apnea. Predicting airway obstruction would allow the safe management of sedative patients to prevent intraoperative hypoxia. This study was designed to check the correlation between the STOP-Bang score and oxygen saturation (SpO2) during sedation and confirm the availability of the STOP-Bang questionnaire as a preoperative exam for predicting the incidence of hypoxia in sedative patient management. METHODS: This study included 56 patients who received spinal anesthesia. The pre-anesthesia evaluation was conducted using the STOP-Bang questionnaire. The patients were under spinal anesthesia with an average block level of T10. Dexmedetomidine was infused with a loading dose of 1 µg/kg over 10 min and a maintenance dose of 0.5 µg/kg/h until the end of the procedure. The SpO2 of the patients was recorded every 5 min. RESULTS: The STOP-Bang score was negatively correlated with the lowest SpO2 (coefficient = -0.774, 95% confidence interval [CI]: -0.855 to -0.649, standard error [SE] = 0.054, P < 0.001). The item of "observed apnea" was the most correlated one with hypoxic events (odds ratio = 6.00, 95% CI: 1.086 to 33.145). CONCLUSIONS: The STOP-BANG score was significantly correlated with the lowest SpO2 during spinal anesthesia, which enabled the prediction of meaningful hypoxia before it occurred in the sedated patients.

The human ß-globin enhancer LCR HS2 plays a role in forming a TAD by activating chromatin structure at neighboring CTCF sites.

The human ß-globin locus control region (LCR) hypersensitive site 2 (HS2) is one of enhancers for transcription of the ß-like globin genes in erythroid cells. Our previous study showed that the LCR HS2 has active chromatin structure before transcriptional induction of the ß-globin gene, while another enhancer LCR HS3 is activated by the induction. To compare functional difference between them, we deleted each HS (ΔHS2 and ΔHS3) from the human ß-globin locus in hybrid MEL/ch11 cells. Deletion of either HS2 or HS3 dramatically diminished the ß-globin transcription and disrupted locus-wide histone H3K27ac and chromatin interaction between LCR HSs and gene. Surprisingly, ΔHS2 weakened interactions between CTCF sites forming the ß-globin topologically associating domain (TAD), while ΔHS3 did not. CTCF occupancy and chromatin accessibility were reduced at the CTCF sites in the ΔHS2 locus. To further characterize the HS2, we deleted the maf-recognition elements for erythroid activator NF-E2 at HS2. This deletion decreased the ß-globin transcription and enhancer-promoter interaction, but did not affect interactions between CTCF sites for the TAD. In light of these results, we propose that the HS2 has a role in forming a ß-globin TAD by activating neighboring CTCF sites and this role is beyond typical enhancer activity.

Effect of chargrilled flavoring on the sensory perception and consumer acceptability of bulgogi (Korean barbecued beef).

As the home-meal replacement food industry grows, there is an increasing need for smoky flavorings that can satisfy the diverse tastes of consumers. In particular, the industry requires chargrilled flavorings that complement Korean foods. In this study, chargrilled flavoring was applied to bulgogi (Korean barbecued beef) and its effects on consumer liking, sensory perception, familiarity, and flavor congruency with the bulgogi were investigated. Eight formulations (one control and seven flavorings) were tested by 78 Korean subjects. A rate-all-that-apply test was conducted to profile the sensory attributes of the food from the consumers' perspectives. The samples with weaker woody and smoky flavors were preferred; the samples with strong woody and smoky flavors were perceived as being artificial and Western-styled, as well as less familiar and incongruent with bulgogi. This study shows that flavorings that are congruent with a food system can improve consumer liking and the perception of familiarity.

Concentration-dependent oscillation of specific loss power in magnetic nanofluid hyperthermia.

Magnetic dipole coupling between the colloidal superparamagnetic nanoparticles (SPNPs) depending on the concentration has been paid significant attention due to its critical role in characterizing the Specific Loss Power (SLP) in magnetic nanofluid hyperthermia (MNFH). However, despite immense efforts, the physical mechanism of concentration-dependent SLP change behavior is still poorly understood and some contradictory results have been recently reported. Here, we first report that the SLP of SPNP MNFH agent shows strong concentration-dependent oscillation behavior. According to the experimentally and theoretically analyzed results, the energy competition among the magnetic dipole interaction energy, magnetic potential energy, and exchange energy, was revealed as the main physical reason for the oscillation behavior. Empirically demonstrated new finding and physically established model on the concentration-dependent SLP oscillation behavior is expected to provide biomedically crucial information in determining the critical dose of an agent for clinically safe and highly efficient MNFH in cancer clinics.

A Study on the Mechanical Properties of an Automobile Part Additively Printed through Periodic Layer Rotation Strategies.

In metal product manufacturing, additive manufacturing (AM) is a method that has the advantage of fabricating complex shapes and customized production, unlike existing machining methods. However, owing to the characteristics of the AM process, anisotropy of macrostructure occurs because of various causes such as the scan direction, melting, fusion, and cooling of the powdered material. The macrostructure anisotropy is realized from the scan direction, and when a single layer is stacked in one direction, it is expressed as orthogonal anisotropy. Here, the classical lamination theory is applied to simply calculate the individual orthotropic layers by superimposing them. Through this, the authors analyzed whether the mechanical properties of the product are isotropically expressed with a periodic layer rotation strategy. To determine if the mechanical properties can be reasonably considered to be isotropic, a shock absorber mount for a vehicle was manufactured by AM. The tensile and vibration test performed on the product was compared with the finite element analysis and experimental results. As a result of the comparison, it was confirmed that the macroscopically of the product was considered isotropic as the load-displacement diagram and the fracture location coincided, as well as the natural frequency and mode shape.