Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion.

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors.

Biphasic Regulation of Apoptosis Following Gastric Irreversible Electroporation Using Tissue Immunohistochemistry of Activated Caspase-3 with TUNEL Method.

The regulation of apoptosis is the primary goal of ablation therapy. Irreversible electroporation (IRE) is a promising non-thermal tissue ablation-based therapy that induces apoptosis by manipulating electrical conditions. This study aimed to investigate IRE-induced gastric tissue apoptosis in response to changes in the electric field intensity, followed by the repair process. Among the 52 rats used in this study, 24 were used to explore apoptosis, and 28 were used to study regeneration. The apoptosis-to-necrosis ratio of the electrical field strength was evaluated using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3 immunohistochemistry. The size of IRE-induced ulcers in the gastric tissue continuously increased with increasing electrical intensity (r2 = 0.830, p < 0.001). The level of apoptosis gradually decreased after peaking at 200 V (1000 V/cm). The size of the 400 V-ablated ulcers continued to decrease, and they were not visible by day 14. The proliferation and migration of epithelial cells with fibroblasts were observed on day 3 and augmented on day 7 post-ablation. This investigation demonstrated the biphasic activation of apoptosis with respect to the electrical field strength. Visually and histologically, IRE-induced gastric ulcers demonstrated complete tissue regeneration after two weeks.

Effects of functional nutrients on chicken intestinal epithelial cells induced with oxidative stress.

The objective of this study was to investigate the protective effects of functional nutrients including various functional amino acids, vitamins, and minerals on chicken intestinal epithelial cells (cIECs) treated with oxidative stress. The cIECs were isolated from specific pathogen free eggs. Cells were exposed to 0 mM supplement (control), 20 mM threonine (Thr), 0.4 mM tryptophan (Trp), 1 mM glycine (Gly), 10 µM vitamin C (VC), 40 µM vitamin E (VE), 5 µM vitamin A (VA), 34 µM chromium (Cr), 0.42 µM selenium (Se), and 50 µM zinc (Zn) for 24 h with 6 replicates for each treatment. After 24 h, cells were further incubated with fresh culture medium (positive control, PC) or 1 mM H2O2 with different supplements (negative control, NC and each treatment). Oxidative stress was measured by cell proliferation, whereas tight junction barrier function was analyzed by fluorescein isothiocyanate (FITC)-dextran permeability and transepithelial electrical resistance (TEER). Results indicated that cell viability and TEER values were less (p < 0.05) in NC treatments with oxidative stress than in PC treatments. In addition, FITC-dextran values were greater (p < 0.05) in NC treatments with oxidative stress than in PC treatments. The supplementations of Thr, Trp, Gly, VC, and VE in cells treated with H2O2 showed greater (p < 0.05) cell viability than the supplementation of VA, Cr, Se, and Zn. The supplementations of Trp, Gly, VC, and Se in cells treated with H2O2 showed the least (p < 0.05) cellular permeability. In addition, the supplementation of Thr, VE, VA, Cr, and Zn in cells treated with H2O2 decreased (p < 0.05) cellular permeability. At 48 h, the supplementations of Thr, Trp, and Gly in cells treated with H2O2 showed the greatest (p < 0.05) TEER values among all treatments, and the supplementations of VC and VE in cells treated with H2O2 showed greater (p < 0.05) TEER values than the supplementations of VA, Cr, Se, and Zn in cells treated with H2O2. In conclusion, Thr, Trp, Gly, and VC supplements were effective in improving cell viability and intestinal barrier function of cIECs exposed to oxidative stress.

Research Note: Effect of increasing fat supplementation in diets on productive performance, egg quality, and fatty liver incidence in laying hens throughout the entire laying cycle.

This study aimed to investigate the effect of increasing fat supplementation in diets on productive performance, egg quality, and fatty liver incidence in laying hens during the entire laying cycle. A total of three hundred eighty-four 18-wk-old Hy-Line Brown laying hens were randomly allotted to 1 of 3 dietary treatments with 8 replicates for a 52-wk feeding trial. Each replicate comprised 16 consecutive cages with 1 hen per cage. The experimental diets were prepared by supplementing 0, 1.5, or 3.0% tallow to a basal diet, but all nutrients and energy in 3 diets were formulated to be equalized according to the recommended nutrient and energy concentrations at each phase of laying hens. Results indicated that increasing fat supplementation in diets decreased (linear, P < 0.01) feed conversion ratio (FCR) by increased egg mass (linear, P < 0.05) but decreased feed intake (linear and quadratic, P < 0.05) in laying hens during overall periods. Increasing fat supplementation in diets decreased (linear and quadratic, P < 0.05) egg yolk color during overall periods. Increasing fat supplementation in diets had no effects on liver color and hemorrhagic score measured at 60 wk (phase 3) and 70 wk of age (phase 4) without affecting hepatic fat concentrations during overall periods. However, the relative abdominal fat weight in laying hens was increased (linear and quadratic, P < 0.05) during overall periods by increasing fat supplementation in diets. In conclusion, increasing fat supplementation up to 3.0% in diets improves FCR with no impacts on fatty liver incidence and economics in laying hens throughout the entire laying cycle.

Kondo interaction in FeTe and its potential role in the magnetic order.

Finding d-electron heavy fermion states has been an important topic as the diversity in d-electron materials can lead to many exotic Kondo effect-related phenomena or new states of matter such as correlation-driven topological Kondo insulator. Yet, obtaining direct spectroscopic evidence for a d-electron heavy fermion system has been elusive to date. Here, we report the observation of Kondo lattice behavior in an antiferromagnetic metal, FeTe, via angle-resolved photoemission spectroscopy, scanning tunneling spectroscopy and transport property measurements. The Kondo lattice behavior is represented by the emergence of a sharp quasiparticle and Fano-type tunneling spectra at low temperatures. The transport property measurements confirm the low-temperature Fermi liquid behavior and reveal successive coherent-incoherent crossover upon increasing temperature. We interpret the Kondo lattice behavior as a result of hybridization between localized Fe 3dxy and itinerant Te 5pz orbitals. Our observations strongly suggest unusual cooperation between Kondo lattice behavior and long-range magnetic order.

Characterization of gut microbiota in mouse models of aging and sarcopenia.

Gut microbiota play vital roles in the maintenance of human health and in various diseases. We aimed to investigate the association of gut microbiota with aging and sarcopenia. This study contained two experimental designs using the ICR mouse model for 1) determining the association between aging and gut microbiota (by analyzing murine fecal samples) and 2) determining the association between sarcopenia and gut microbiota in mice treated with microorganisms or dexamethasone. The composition of the gut microbiota was determined by next-generation sequencing. Marginally significant differences were observed in taxon composition of the gut microbiota depending on age; particularly, the abundance of the genusAlistipes increased with increasing age. In addition, the abundance of the class Bacteroidia decreased with increasing age, whereas that of the genus Oscillibacter increased. The microbiome composition differed between young mice and aging mice with sarcopenia. Moreover, the gut microbiota in aging and sarcopenia showed altered abundances of Alistipes, Lachnospiraceae, and Bacteroides. Although the sample size was small, these results point to similarities in the gut microbiota between aging and sarcopenia and to differences between young and old individuals. The results on gut microbiota obtained in this study form a basis for studying the development of sarcopenia in geriatric animal models in the future.

Determination of safe levels and toxic levels for feed hazardous materials in broiler chickens: a review.

Feed safety is needed to produce and provide safe animal feeds for consumers, animals, and the environment. Although feed safety regulations have been set for each country, there is a lack of clear feed safety regulations for each livestock. Feed safety regulations are mainly focused on heavy metals, mycotoxins, and pesticides. Each country has different safe levels of hazardous materials in diets. Safe levels of hazardous materials in diets are mostly set for mixed diets of general livestock. Although there is a difference in the metabolism of toxic materials among animals, the safe level of feed is not specific for individual animals. Therefore, standardized animal testing methods and toxicity studies for each animal are needed to determine the correct safe and toxic levels of hazardous materials in diets. If this goal is achieved, it will be possible to improve livestock productivity, health, and product safety by establishing appropriate feed safety regulations. It will also provide an opportunity to secure consumer confidence in feed and livestock products. Therefore, it is necessary to establish a scientific feed safety evaluation system suitable for each country's environment. The chance of outbreaks of new hazardous materials is increasing. Thus, to set up appropriate toxic levels or safe levels in feed, various toxicity methods have been used to determine toxic levels of hazardous materials for humans and animals. Appropriate toxic testing methods should be developed and used to accurately set up and identify toxicity and safe levels in food and feed.

Gapless superconductivity in Nb thin films probed by terahertz spectroscopy.

Time reversal symmetry (TRS) breaking often generates exotic quantum phases in condensed matter. In superconductors, TRS breaking by an external magnetic field not only suppresses superconductivity but also leads to a novel quantum state called the gapless superconducting state. Here we show that magneto-terahertz spectroscopy provides us with a rare opportunity to access and explore the gapless superconducting state of Nb thin films. We present the complete functional form of the superconducting order parameter for an arbitrary magnetic field, for which a fully self-consistent theory is, surprisingly, yet unavailable. We observe a Lifshitz topological phase transition with a vanishing quasiparticle gap everywhere on the Fermi surface, whereas the superconducting order parameter smoothly crosses over from the gapped to the gapless regime. Our observation of the magnetic pair-breaking effects in Nb challenges traditional perturbative theories and opens a pathway to further exploring and manipulating the exotic state of gapless superconductivity.

Assessment of efficacy and safety of advanced endoscopic irreversible electroporation catheter in the esophagus.

Nonthermal irreversible electroporation (NTIRE) is emerging as a promising tissue ablation technique. However, maintaining irreversible electroporation (IRE) electrodes against displacement during strong esophageal spasms remains an obstacle. The present study aimed to evaluate the efficacy and safety of newly designed balloon-type endoscopic IRE catheters. Six pigs were randomly allocated to each catheter group, and each pig was subjected to four ablations at alternating voltages of 1500 V and 2000 V. Esophagogastroscopy was performed during the IRE. The ability of balloon-type catheters to execute complete IRE with 40 pulses was assessed. The success rate was higher for the balloon-type catheter than that for the basket-type (12/12 [100%] vs. 2/12 [16.7%], p < 0.001). Following gross inspection and histologic analysis of the 1500-V vs. 2000-V balloon-type catheter revealed a larger mucosal damage area (105.3 mm2 vs. 140.8 mm2, p = 0.004) and greater damage depth (476 µm vs. 900 µm, p = 0.02). Histopathology of the ablated tissue revealed separated epithelium, inflamed lamina propria, congested muscularis mucosa, necrotized submucosa, and disorganized muscularis propria. Balloon-type catheters demonstrated efficacy, achieving full electrical pulse sequences under NTIRE conditions, and a safe histological profile below 2000 V (1274 V/cm). Optimal electrical conditions and electrode arrays pose ongoing challenges.

Analysis of changes in antibiotic resistance in the human body using an in vitro digestion model incorporating human gut microbiota.

Residual antibiotics may affect human health by increasing challenges related to infection treatment due to antibiotic resistance development. Hence, determining whether residual antibiotics in the body can lead to antibiotic resistance is important. We developed a model to predict possible antibiotic resistance caused by residual antibiotics by simulating human digestion in vitro. Increased antibiotic resistance was found to be dependent on the digestion process. Ethical prediction of antibiotic resistance using fewer animals and no humans was possible by simulating the internal environment. Thus, preliminary studies to monitor antibiotic resistance that can affect human health may be safely conducted using this model.

Giant and highly anisotropic magnetocaloric effects in single crystals of disordered-perovskite RCr0.5Fe0.5O3 (R = Gd, Er).

Magnetic anisotropy is crucial in examining suitable materials for magnetic functionalities because it affects their magnetic characteristics. In this study, disordered-perovskite RCr0.5Fe0.5O3 (R = Gd, Er) single crystals were synthesized and the influence of magnetic anisotropy and additional ordering of rare-earth moments on cryogenic magnetocaloric properties was investigated. Both GdCr0.5Fe0.5O3 (GCFO) and ErCr0.5Fe0.5O3 (ECFO) crystallize in an orthorhombic Pbnm structure with randomly distributed Cr3+ and Fe3+ ions. In GCFO, the long-range order of Gd3+ moments emerges at a temperature of TGd (the ordering temperature of Gd3+ moments) = 12 K. The relatively isotropic nature of large Gd3+ moment originating from zero orbital angular momentum exhibits giant and virtually isotropic magnetocaloric effect (MCE), with a maximum magnetic entropy change of [Formula: see text] ≈ 50.0 J/kg·K. In ECFO, the highly anisotropic magnetizations result in a large rotating MCE characterized by a rotating magnetic entropy change [Formula: see text] = 20.8 J/kg·K. These results indicate that a detailed understanding of magnetically anisotropic characteristics is the key for exploring improved functional properties in disordered perovskite oxides.

Electrical Transport Properties Driven by Unique Bonding Configuration in γ-GeSe.

Group IV monochalcogenides have recently shown great potential for their thermoelectric, ferroelectric, and other intriguing properties. The electrical properties of group IV monochalcogenides exhibit a strong dependence on the chalcogen type. For example, GeTe exhibits high doping concentration, whereas S/Se-based chalcogenides are semiconductors with sizable bandgaps. Here, we investigate the electrical and thermoelectric properties of γ-GeSe, a recently identified polymorph of GeSe. γ-GeSe exhibits high electrical conductivity (∼106 S/m) and a relatively low Seebeck coefficient (9.4 µV/K at room temperature) owing to its high p-doping level (5 × 1021 cm-3), which is in stark contrast to other known GeSe polymorphs. Elemental analysis and first-principles calculations confirm that the abundant formation of Ge vacancies leads to the high p-doping concentration. The magnetoresistance measurements also reveal weak antilocalization because of spin-orbit coupling in the crystal. Our results demonstrate that γ-GeSe is a unique polymorph in which the modified local bonding configuration leads to substantially different physical properties.

Spin-flip-driven anomalous Hall effect and anisotropic magnetoresistance in a layered Ising antiferromagnet.

The influence of magnetocrystalline anisotropy in antiferromagnets is evident in a spin flip or flop transition. Contrary to spin flops, a spin-flip transition has been scarcely presented due to its specific condition of relatively strong magnetocrystalline anisotropy and the role of spin-flips on anisotropic phenomena has not been investigated in detail. In this study, we present antiferromagnet-based functional properties on an itinerant Ising antiferromagnet Ca0.9Sr0.1Co2As2. In the presence of a rotating magnetic field, anomalous Hall conductivity and anisotropic magnetoresistance are demonstrated, the effects of which are maximized above the spin-flip transition. Moreover, a joint experimental and theoretical study is conducted to provide an efficient tool to identify various spin states, which can be useful in spin-processing functionalities.

Effects of dietary organic or inorganic iron concentrations on productive performance, egg quality, blood measurements, and tissue iron concentrations in aged laying hens.

The objective of the current experiment was to investigate the effects of dietary organic or inorganic iron (Fe) concentrations on productive performance, egg quality, blood measurements, and tissue Fe concentrations in aged laying hens. A total of three hundred fifty 60-week-old Hy-Line Brown laying hens were allotted to one of five dietary treatments with seven replicates. Each replicate had 10 consecutive cages. Organic Fe (Fe-Gly) or inorganic Fe (FeSO4 ) was added to the basal diet at the levels of 100 or 200 mg/kg Fe. Diets were fed on an ad libitum basis for 6 weeks. Results indicated that supplementation of organic or inorganic Fe in diets increased (p < 0.05) eggshell color and feather Fe concentrations compared with no supplementation of Fe in diets. An interaction was found (p < 0.05) between Fe sources and supplemental levels in diets for egg weight, eggshell strength, and Haugh unit. Hens fed diets supplemented with organic Fe had greater (p < 0.05) eggshell color and hematocrit than those fed diets supplemented with inorganic Fe. In conclusion, dietary supplementation of organic Fe increases the eggshell color of aged laying hens. High supplemental levels of organic Fe in diets improve egg weight in aged laying hens.

Effect of dietary concentrations of metabolizable energy and neutral detergent fiber on productive performance, egg quality, fatty liver incidence, and hepatic fatty acid metabolism in aged laying hens.

The objective of the current experiment was to investigate the effect of dietary concentrations of ME and neutral detergent fiber (NDF) on productive performance, egg quality, fatty liver incidence, and hepatic fatty acid metabolism in aged laying hens. A total of three hundred twenty 75-wk-old Hy-Line Brown laying hens were allotted to 1 of 4 dietary treatments with 8 replicates. Each replicate consisted of 10 consecutive cages with 1 hen per cage. The experiment was conducted using a completely randomized design with 2 × 2 factorial arrangement consisting of 2 levels of ME (normal [commercially recommended AMEn levels; 2,730 kcal/kg] and low [50 kcal/kg reduction in AMEn; 2,680 kcal/kg]) and 2 levels of NDF (low [9.01 and 9.61%; normal-ME and low-ME diets, respectively] and high [12.57 and 13.42%; normal-ME and low-ME diets, respectively]) in the diet. The diets and water were provided to hens on an ad libitum basis for 12 wk. Results indicated that no interactions between dietary concentrations of ME and NDF were observed for all measurements except for egg yolk color, eggshell thickness, and 2 hepatic gene expressions (i.e., carnitine palmitoyl transferase 1A and malic enzyme). For the main effects, increasing NDF concentrations in diets increased (P < 0.05) feed intake without affecting other productive performance. Hens fed normal-ME and high-NDF diets showed the darkest (P < 0.05) egg yolk color among those fed treatment diets, showing an interaction (P < 0.05). Increasing NDF concentrations in low-ME diets did not influence eggshell thickness, but those in normal-ME diets increased eggshell thickness in laying hens, showing an interaction (P < 0.05). For the main effects, increasing concentrations of dietary NDF or ME reduced (P < 0.05) hepatic fat concentrations with decreasing expressions in several genes related to fatty acid synthesis. In conclusion, increasing NDF concentrations in commercially-recommended ME diets decrease hepatic fat concentrations in aged laying hens, and therefore, may have a preventative effect on the fatty liver development in aged laying hens.

Independent effect of body mass index variation on amyloid-ß positivity.

Objectives: The relationship of body mass index (BMI) changes and variability with amyloid-ß (Aß) deposition remained unclear, although there were growing evidence that BMI is associated with the risk of developing cognitive impairment or AD dementia. To determine whether BMI changes and BMI variability affected Aß positivity, we investigated the association of BMI changes and BMI variability with Aß positivity, as assessed by PET in a non-demented population. Methods: We retrospectively recruited 1,035 non-demented participants ≥50 years of age who underwent Aß PET and had at least three BMI measurements in the memory clinic at Samsung Medical Center. To investigate the association between BMI change and variability with Aß deposition, we performed multivariable logistic regression. Further distinctive underlying features of BMI subgroups were examined by employing a cluster analysis model. Results: Decreased (odds ratio [OR] = 1.68, 95% confidence interval [CI] 1.16-2.42) or increased BMI (OR = 1.60, 95% CI 1.11-2.32) was associated with a greater risk of Aß positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI variability. A greater BMI variability (OR = 1.73, 95% CI 1.07-2.80) was associated with a greater risk of Aß positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI change. We also identified BMI subgroups showing a greater risk of Aß positivity. Conclusion: Our findings suggest that participants with BMI change, especially those with greater BMI variability, are more vulnerable to Aß deposition regardless of baseline BMI. Furthermore, our results may contribute to the design of strategies to prevent Aß deposition with respect to weight control.

Non-invasive cancer detection in canine urine through Caenorhabditis elegans chemotaxis.

Cancer is the leading cause of death in companion animals, and successful early treatment has been a challenge in the veterinary field. We have developed the Non-Invasive Cancer Screening (N.C.S.) Study to perform cancer detection through the analysis of canine urine samples. The test makes use of the strong olfactory system of the nematode Caenorhabditis elegans, which was previously shown to positively respond to urine samples from human cancer patients. We performed a proof-of-concept study to optimize the detection capability in urine samples obtained from dogs with naturally occurring cancers. In this study, we established a scale for identifying the cancer risk based on the magnitude of the chemotaxis index of C. elegans toward a canine urine sample. Through validation, the N.C.S. Study achieved a sensitivity of 85%, showing that it is highly sensitive to indicate the presence of cancer across multiple types of common canine cancers. The test also showed a 90% specificity to cancer samples, indicating a low rate of over-identifying cancer risk. From these results, we have demonstrated the ability to perform low-cost, non-invasive cancer detection in companion animals-a method that can increase the ability to perform cancer diagnosis and treatment.

Evaluation of coated platelets, a subset of highly procoagulant platelets, in healthy dogs and dogs with neoplasia.

OBJECTIVE: To determine if dogs with neoplasia produce more coated platelets, a subpopulation of activated platelets generated by dual stimulation with thrombin and convulxin, a glycoprotein VI agonist, than healthy control dogs. ANIMALS: Client-owned dogs diagnosed with lymphoma (n = 19) or solid tumors (14) and healthy control dogs (14). PROCEDURES: Platelets were stimulated ex vivo with thrombin and convulxin. Flow cytometry was used to quantify the percentage of coated platelets based on high levels of surface fibrinogen. To compare the percentage of coated platelets between the three groups, an ANOVA was performed followed by pairwise 95% confidence intervals (CI) adjusted for multiple comparisons using Tukey's method. RESULTS: We observed a greater mean percentage of coated platelets in dogs with solid tumors, compared with healthy control dogs, by 10.9 percentage points (95% CI: -1.0, 22.8), and a mean percentage of coated platelets in dogs with lymphoma that was less than healthy control dogs by 0.3 percentage points (95% CI: -11.4, 10.8). CLINICAL RELEVANCE: This study provides the first data-based evidence that dogs with solid tumors may have a greater mean coated platelet percentage when compared with healthy control dogs, although there is overlap between groups. Further studies are needed investigating coated platelets in specific subsets of neoplasia and investigating additional mechanisms of hypercoagulability in dogs with neoplasia.