Echocardiographic diagnosis of aorto-left ventricular tunnel with supravalvular pulmonic stenosis in a Shih-tzu dog.

Background: The aorto-left ventricular tunnel (ALVT) is a congenital extracardiac channel that connects the ascending aorta to the left ventricle. Case Description: A 2-year-old Shih-tzu dog presented with mild exercise intolerance. Echocardiography revealed an abnormal slit-like tunnel structure connecting the ascending aorta to the left ventricle, with diastolic blood flow from the aorta to the left ventricle. Echogenic membranous stenosis was observed in the main pulmonary artery. Based on these findings, the dog was diagnosed with ALVT and type I supravalvular pulmonic stenosis. Conclusion: This is the first case report of ALVT in veterinary medicine that describes diagnostic imaging findings. ALVT should be considered in dogs with an aortic regurgitation murmur and can be detected by echocardiography.

Increased radiographic opacity in the region of the gallbladder can be identified in dogs with large amounts of gallbladder sediment, sludge balls, and gallbladder mucocele.

Increased soft-tissue opacity in the region of the canine gallbladder is incidentally detected on radiographs. We hypothesized that there is a difference in the detection of gallbladder sediment on radiographs depending on the amount or mobility of the sediment. In this retrospective and analytical study, we aimed to assess the ultrasonographic features of gallbladder sediment that were detected radiographically. We also aimed to assess the differences in the detection of increased opacity of the gallbladder between radiographic views. We included 223 dogs that underwent thoracic radiography, abdominal radiography, and gallbladder ultrasonography. Ultrasonographic images of the gallbladder were divided into five groups: group 1, gravity-dependent sediment occupying < 50% of the gallbladder; group 2, gravity-dependent sediment occupying ≥50%; group 3, sediment attached to the gallbladder wall; group 4, sludge ball; and group 5, gallbladder mucocele. Dogs showing increased opacity on subjective assessment of any radiographic view were recorded, and the sensitivity of radiographic views for detecting gallbladder sediment was analyzed. Of 168 dogs with gallbladder sediment, 37 had increased opacity on at least one radiographic projection. The frequency was compared as a percentage within each category, and Group 4 was the highest percentage with increased radiographic gallbladder opacity, followed by Groups 2 and 5. The sensitivity for detecting increased opacity was highest in the thoracic ventrodorsal view. Thus, in dogs with increased gallbladder opacity on radiographs, large amounts of gallbladder sediment, sludge balls, and gallbladder mucocele should be considered differential diagnoses. In addition, the thoracic ventrodorsal view is recommended to evaluate gallbladder opacity.

Thyroid carcinosarcoma masquerading as a paraesophageal abscess in a Cane Corso dog.

A 12-year-old castrated male Cane Corso dog was presented with cervical swelling, lethargy, anorexia, and cough. An extensive neck mass with necrotic cysts was observed, severely adherent to surrounding tissues. Based on diagnostic imaging including ultrasound, computed tomography, and fine-needle aspiration cytology, paraesophageal abscess was tentatively diagnosed. However, after the mass was surgically removed, a diagnosis of thyroid carcinosarcoma composed of neoplastic cell populations with epithelial and mesenchymal origins was made via histopathology and immunohistochemistry. The dog died of a recurrent mass with pulmonary metastasis 105 d after surgery. This report describes a rare type of canine thyroid cancer, thyroid carcinosarcoma, preoperatively masquerading as an abscess and postoperatively confirmed by histopathology. Key clinical message: Thyroid carcinosarcoma, despite its rarity in dogs, should be included in the differential diagnoses of cervical mass especially with an aggressive progression.

Carcinosarcome thyroïdien déguisé en abcès paraoesophagien chez un chien Cane Corso. Un chien Cane Corso mâle castré de 12 ans a été présenté avec de l'enflure cervicale, de la léthargie, de l'anorexie et une toux. Une masse étendue du cou avec des kystes nécrotiques a été observée, adhérente fortement aux tissus environnants. Sur la base de l'imagerie diagnostique comprenant l'échographie, la tomodensitométrie et la cytologie par aspiration à l'aiguille fine, un abcès paraoesophagien a été provisoirement diagnostiqué. Cependant, après l'ablation chirurgicale de la masse, un diagnostic de carcinosarcome thyroïdien composé de populations de cellules néoplasiques d'origine épithéliale et mésenchymateuse a été posé par histopathologie et immunohistochimie. Le chien est décédé d'une masse récurrente avec métastase pulmonaire 105 jours après la chirurgie. Ce rapport décrit un type rare de cancer de la thyroïde canine, le carcinosarcome thyroïdien, se faisant passer pour un abcès en préopératoire et confirmé en postopératoire par histopathologie.Message clinique clé:Le carcinosarcome thyroïdien, malgré sa rareté chez le chien, doit être inclus dans les diagnostics différentiels de masse cervicale surtout à évolution agressive.(Traduit par Dr Serge Messier).

Scalable manufacturing of high-index atomic layer-polymer hybrid metasurfaces for metaphotonics in the visible.

Metalenses are attractive alternatives to conventional bulky refractive lenses owing to their superior light-modulating performance and sub-micrometre-scale thicknesses; however, limitations in existing fabrication techniques, including high cost, low throughput and small patterning area, have hindered their mass production. Here we demonstrate low-cost and high-throughput mass production of large-aperture visible metalenses using deep-ultraviolet argon fluoride immersion lithography and wafer-scale nanoimprint lithography. Once a 12″ master stamp is imprinted, hundreds of centimetre-scale metalenses can be fabricated using a thinly coated high-index film to enhance light confinement, resulting in a substantial increase in conversion efficiency. As a proof of concept, an ultrathin virtual reality device created with the printed metalens demonstrates its potential towards the scalable manufacturing of metaphotonic devices.

One-step printable platform for high-efficiency metasurfaces down to the deep-ultraviolet region.

A single-step printable platform for ultraviolet (UV) metasurfaces is introduced to overcome both the scarcity of low-loss UV materials and manufacturing limitations of high cost and low throughput. By dispersing zirconium dioxide (ZrO2) nanoparticles in a UV-curable resin, ZrO2 nanoparticle-embedded-resin (nano-PER) is developed as a printable material which has a high refractive index and low extinction coefficient from near-UV to deep-UV. In ZrO2 nano-PER, the UV-curable resin enables direct pattern transfer and ZrO2 nanoparticles increase the refractive index of the composite while maintaining a large bandgap. With this concept, UV metasurfaces can be fabricated in a single step by nanoimprint lithography. As a proof of concept, UV metaholograms operating in near-UV and deep-UV are experimentally demonstrated with vivid and clear holographic images. The proposed method enables repeat and rapid manufacturing of UV metasurfaces, and thus will bring UV metasurfaces more close to real life.

The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of Nelumbo nucifera Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy.

Muscle atrophy is characterized by a decline in muscle mass and function. Excessive glucocorticoids in the body due to aging or drug treatment can promote muscle wasting. In this study, we investigated the preventive effect of Nelumbo nucifera leaf (NNL) ethanolic extract on muscle atrophy induced by dexamethasone (DEX), a synthetic glucocorticoid, in mice and its underlying mechanisms. The administration of NNL extract increased weight, cross-sectional area, and grip strength of quadriceps (QD) and gastrocnemius (GA) muscles in DEX-induced muscle atrophy in mice. The NNL extract administration decreased the expression of muscle atrophic factors, such as muscle RING-finger protein-1 and atrogin-1, and autophagy factors, such as Beclin-1, microtubule-associated protein 1A/1B-light chain 3 (LC3-I/II), and sequestosome 1 (p62/SQSTM1) in DEX-injected mice. DEX injection increased the protein expression levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), cleaved-caspase-1, interleukin-1beta (IL-1ß), and cleaved-gasdermin D (GSDMD), which were significantly reduced by NNL extract administration (500 mg/kg/day). In vitro studies using C2C12 myotubes also revealed that NNL extract treatment inhibited the DEX-induced increase in autophagy factors, pyroptosis-related factors, and NF-κB. Overall, the NNL extract prevented DEX-induced muscle atrophy by downregulating the ubiquitin-proteasome system, autophagy pathway, and GSDMD-mediated pyroptosis pathway, which are involved in muscle degradation.

Assessment of the biofilm-forming ability on solid surfaces of periprosthetic infection-associated pathogens.

Biofilm formation is one of the leading causes of complications after surgery in clinical settings. In this study, we profiled the biofilm-forming ability of various periprosthetic infection-associated pathogens on medically relevant surfaces, polystyrene (PS) and titanium (Ti). We also explored how a specific environmental stressor, epigallocatechin gallate (EGCG), affected biofilm formation. First, Congo red tests revealed that all microorganisms formed biofilms within 72 h. Then, the amounts of biofilm formation on PS at 24, 48 and 72 h and also on a Ti plate for 72 h were determined. Some microbes preferred one surface over the other, whereas other microbes formed consistent levels of biofilm regardless of the surface material. Staphylococcus lugdunenensis was the most potent, while Enterococcus faecalis and Staphylococcus aureus were the weakest. Bacterial adhesion to hydrocarbon (BATH) tests indicated that the biofilm-forming abilities were not directly correlated with cell surface hydrophobicity (CSH). Finally, an external signal, EGCG, was applied to challenge the biofilm formation of each microorganism. EGCG regulated each microorganism's ability differently, though the change was consistent across surfaces for most pathogens. This study can help a better understanding of a broad spectrum of periprosthetic infection-associated pathogens by relative comparison of their biofilm-forming abilities.

Hierarchical Co-Pi Clusters/Fe2O3 Nanorods/FTO Micropillars 3D Branched Photoanode for High-Performance Photoelectrochemical Water Splitting.

In this study, an efficient hierarchical Co-Pi cluster/Fe2O3 nanorod/fluorine-doped tin oxide (FTO) micropillar three-dimensional (3D) branched photoanode was designed for enhanced photoelectrochemical performance. A periodic array of FTO micropillars, which acts as a highly conductive "host" framework for uniform light scattering and provides an extremely enlarged active area, was fabricated by direct printing and mist-chemical vapor deposition (CVD). Fe2O3 nanorods that act as light absorber "guest" materials and Co-Pi clusters that give rise to random light scattering were synthesized via a hydrothermal reaction and photoassisted electrodeposition, respectively. The hierarchical 3D branched photoanode exhibited enhanced light absorption efficiency because of multiple light scattering, which was a combination of uniform light scattering from the periodic FTO micropillars and random light scattering from the Fe2O3 nanorods. Additionally, the large surface area of the 3D FTO micropillar, together with the surface area provided by the one-dimensional Fe2O3 nanorods, contributed to a remarkable increase in the specific area of the photoanode. Because of these enhancements and further improvements facilitated by decoration with a Co-Pi catalyst that enhanced water oxidation, the 3D branched Fe2O3 photoanode achieved a photocurrent density of 1.51 mA cm-2 at 1.23 VRHE, which was 5.2 times higher than that generated by the non-decorated flat Fe2O3 photoanode.

Gomisin G improves muscle strength by enhancing mitochondrial biogenesis and function in disuse muscle atrophic mice.

Disuse muscle atrophy is characterized by a decrease in muscle mass and strength and an increase in glycolytic muscle fiber type. Although Schisandra chinensis extract has beneficial effects on muscle atrophy induced by various conditions (e.g., dexamethasone and aging), the effect of gomisin G, a lignan component of S. chinensis, on disuse muscle atrophy is unclear. Here, we induced disuse muscle atrophy through wire immobilization of the hind legs in mice followed by the oral administration of gomisin G. The cross-sectional area and muscle strength in disuse muscle atrophic mice were increased by gomisin G; however, the total muscle mass did not increase. Gomisin G decreased the expression of muscle atrophic factors (myostatin, atrogin-1, and MuRF1) but increased the expression of protein synthesis factors (mTOR and 4E-BP1). In H2O2-treated C2C12 myotubes, the level of puromycin incorporation (as a marker of protein synthesis) gradually increased in a dose-dependent manner by gomisin G. Furthermore, gomisin G induced a muscle fiber switch from fast-type glycolytic fibers (type 2B) to slow-type oxidative fibers (type I, 2A) in the gastrocnemius (GA) muscle as proved a decrease in the expression of TnI-FS and an increase in the expression of TnI-SS. Gomisin G increased mitochondrial DNA content and ATP levels in the GA muscle and COX activity in H2O2-treated C2C12 myotubes, improving mitochondrial function. Mechanistically, mitochondrial biogenesis is regulated by gomisin G via the Sirt 1/PGC-1α signaling pathway, targeting NRF1 and TFAM. These data suggest that gomisin G has a potential therapeutic effect on disuse muscle atrophy.

Synthesis and CO2 Capture of Porous Hydrogel Particles Consisting of Hyperbranched Poly(amidoamine)s.

We successfully synthesized new macroporous hydrogel particles consisting of hyperbranched poly(amidoamine)s (HPAMAM) using the Oil-in-Water-in-Oil (O/W/O) suspension polymerization method at both the 50 mL flask scale and the 5 L reactor scale. The pore sizes and particle sizes were easily tuned by controlling the agitation speeds during the polymerization reaction. Since O/W/O suspension polymerization gives porous architecture to the microparticles, synthesized hydrogel particles having abundant amine groups inside polymers exhibited a high CO2 absorption capacity (104 mg/g) and a fast absorption rate in a packed-column test.

Thermally-curable nanocomposite printing for the scalable manufacturing of dielectric metasurfaces.

Metasurfaces consisting of artificially designed meta-atoms have been popularized recently due to their advantages of amplitude and phase of light control. However, the electron beam lithography method for metasurface fabrication has high cost and low throughput, which results in a limitation for the fabrication of metasurfaces. In this study, nanocomposite printing technology is used to fabricate high-efficiency metasurfaces with low cost. To demonstrate the efficiency of the proposed fabrication method, a metahologram is designed and fabricated using a nanocomposite. The metahologram exhibits conversion efficiencies of 48% and 35% at wavelengths of 532 and 635 nm, respectively. The nanocomposite is composed of polymers with nanoparticles, so durability tests are also performed to evaluate the effects of temperature and humidity on the metasurfaces. The test verifies that at temperatures below the glass transition temperature of the base resin, the nanostructures do not collapse, so the efficiency of the metasurfaces remains almost the same. The surrounding humidity does not affect the nanostructures at all. Hence, the durability of the nanocomposite metasurfaces can be further enhanced by replacing the base resin, and this nanocomposite printing method will facilitate practical metasurface use at low cost.

Nasopharyngeal collapse can be identified on radiography in healthy male Beagle dogs without cardiopulmonary diseases.

Pharyngeal collapse has been described as a decrease of more than 50% in the diameter of the lumen. However, there has been no study on changes in the pharyngeal lumen in clinically normal dogs. The hypothesis of this prospective, observational, and pilot study was that change in nasopharyngeal lumen would be over 50% in Beagle dogs without cardiopulmonary diseases. Thus, we assessed the nasopharyngeal luminal change using cervical radiography in Beagle dogs without respiratory signs or cardiac abnormalities. The study sample included 42 Beagle dogs without cardiopulmonary diseases. Cervical radiographies were acquired during inspiration and expiration, and nasopharyngeal luminal change (%) was calculated. The median nasopharyngeal luminal change was 16.6%, and nasopharyngeal luminal change over 50% was identified in two dogs. The nasopharyngeal luminal change was significantly associated with body condition score and body weight. There was no correlation between nasopharyngeal luminal change and age. This study revealed that change in nasopharyngeal lumen over 50% can be identified in Beagle dogs without cardiopulmonary diseases and may be over-diagnosed as partial pharyngeal collapse. Further studies for comparing change in nasopharyngeal lumen between clinically normal dogs and dogs with respiratory signs are warranted.

Ultrasonographic patterns, clinical findings, and prognostic variables in dogs from Asia with gallbladder mucocele.

BACKGROUND: Gallbladder mucocele (GBM) is a common biliary disorder in dogs that can be categorized into 6 types, but the value of this classification scheme remains unknown. Cholecystectomy is associated with high death rates and warrants additional interrogation. OBJECTIVES: Investigate the clinical value of ultrasonographic diagnosis of type of GBM and identify prognostic factors in dogs with GBM undergoing cholecystectomy. ANIMALS: Two hundred sixteen dogs. METHODS: Retrospective cohort study. Dogs with GBM diagnosed from 2014 to 2019 at 6 veterinary referral hospitals in Asia. Ultrasonogram images were reviewed and a GBM type (ie, types I-VI) assigned. RESULTS: Dogs with GBM type V as compared to I (OR, 8.6; 95% CI, 2.6-27.8; P < .001) and III (OR, 10.0; 95% CI, 2.5-40.8; P = .001), and dogs with type VI compared to I (OR, 10.5; 95% CI, 1.8-61.2; P = .009) and III (OR, 12.3; 95% CI, 1.8-83.9; P = .01) were more likely to exhibit signs of biliary tract disease. Independent predictors of death after cholecystectomy included age (OR, 2.81; 95% CI, 1.41-5.59; P = .003) and intraoperative systolic blood pressure (SBP) nadir. There was an interaction between SBP nadir and gallbladder rupture; SBP nadir in dogs with (OR, 0.92; 95% CI, 0.89-0.94; P < .001) and without (OR, 0.88; 95% CI, 0.82-0.93; P < .001) gallbladder rupture. CONCLUSION AND CLINICAL IMPORTANCE: Increasing developmental stage of GBM could be associated with an increased likelihood of biliary tract related clinical signs. Nadir SBP deserves further investigation as a prognostic or potentially modifiable variable, particularly in the presence of gallbladder rupture.

Ethanol Extract of Liriope platyphylla Root Attenuates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice via Regulation of Lipogenesis and Lipid Uptake.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder that causes excess lipid accumulation in the liver and is the leading cause of end-stage liver disease. Liriope platyphylla is a medicinal herb that has long been used to treat cough, obesity, and diabetes. However, the effect of Liriope platyphylla on NAFLD has not been studied. The aim of this study was to investigate the effect of Liriope platyphylla root ethanolic extract (LPE) on hepatic lipid accumulation in high-fat diet (HFD)-induced obese mice. Six-week-old C57BL/6 male mice were fed a HFD for 8 weeks and then treated with LPE (100 or 250 mg/kg/day) by oral gavage for another 8 weeks. Body weight gain and liver weight were significantly lower in the 250 mg/kg LPE-treated HFD group than in the vehicle-treated HFD group. Histological analysis of liver sections demonstrated that LPE treatment reduced lipid accumulation compared to the vehicle treatment. The serum total cholesterol, AST, and ALT levels significantly decreased in the LPE-treated HFD group compared to those in the vehicle-treated HFD group. The LPE significantly decreases the protein expression levels of SREBP1, ACC, p-ACC, FAS, and SCD1, which are involved in lipogenesis, and PPARγ, CD36/FAT, and FATP5, which are involved in fatty acid uptake, both in vivo and in vitro. Thus, LPE may attenuate HFD-induced NAFLD by decreasing lipid accumulation by inhibiting lipogenesis and fatty acid uptake.

Poly (Amidehydrazide) Hydrogel Particles for Removal of Cu2+ and Cd2+ Ions from Water.

Poly(amidoamine)s (PAMAM) are very effective in the removal of heavy metal ions from water due to their abundant amine and amide functional groups, which have a high binding ability to heavy metal ions. We synthesized a new class of hyperbranched poly(amidehydrazide) (PAMH) hydrogel particles from dihydrazides and N,N'-methylenebisacrylamide (MBA) monomer by using the A2 + B4 polycondensation reaction in an inverse suspension polymerization process. In Cd2+ and Cu2+ ion sorption tests, the synthesized dihydrazide-based PAMH hydrogel particles exhibited sorption capacities of 85 mg/g for copper and 47 mg/g for cadmium. Interestingly, the PAMH showed only a 10% decrease in sorption ability in an acidic condition (pH = 4) compared to the diamine-based hyperbranched PAMAM, which showed a ~90% decrease in sorption ability at pH of 4. In addition, PAMH hydrogel particles remove trace amounts of copper (0.67 ppm) and cadmium (0.5 ppm) in water, below the detection limit.

Dynamic computed tomography evaluation of the nasopharynx in normal Beagle dogs.

Pharyngeal collapsibility has been used as diagnostic criteria in dogs, whereas the normal range and quantitative method have not been studied. Dynamic and static computed tomography (CT) was performed in 23 normal Beagle dogs to quantify the nasopharyngeal collapsibility at different locations. Using dynamic CT, maximum and minimum nasopharyngeal cross-sectional areas (CSAs) were measured at the level of the cranial end of the soft palate, pterygoid hamulus, foramen lacerum, bony labyrinth, and caudal end of the soft palate. The ratio of all maximum and minimum CSA to nasopharyngeal CSA at the level of the caudal hard palate (rCSAmax and rCSAmin) and the nasopharyngeal collapsibility were calculated. The differences of rCSAmax, rCSAmin, and nasopharyngeal collapsibility were analyzed at various locations. The nasopharyngeal collapsibility at the level of foramen lacerum, bony labyrinth, and caudal end of soft palate were higher than the others. At the level of the caudal end of the soft palate, rCSAmin was lower than that of the foramen lacerum and bony labyrinth, whereas rCSAmax at foramen lacerum was higher than that of the caudal end of the soft palate. These results indicated that the nasopharynx at the level of foramen lacerum and caudal end of the soft palate were considered notable locations for evaluating collapsibility. Dynamic CT could show the nasopharyngeal dynamic profile and will be an adequate modality for evaluating nasopharynx. Our results will be helpful for further comparative studies in dogs with and without nasopharyngeal collapse.

Synthesis and anti-diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists.

Type 2 diabetes is characterized by chronic hyperglycemia. Insulin, a hormone secreted from pancreatic ß-cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic α-cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic glucose production. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, inhibition of the glucagon receptor is one strategy for the treatment of hyperglycemia in type 2 diabetes. In this paper, we report a series of biphenylsulfonamide derivatives that were designed, synthesized, and then evaluated by cAMP and hepatic glucose production assays as glucagon receptor antagonists. Of these, compound 7aB-3 decreased glucagon-induced cAMP production and glucagon-induced glucose production in the in vitro assays. Glucagon challenge tests and glucose tolerance tests showed that compound 7aB-3 significantly inhibited glucagon-induced glucose increases and improved glucose tolerance. These results suggest that compound 7aB-3 has therapeutic potential for the treatment of type 2 diabetes.

Downregulation of NKG2DLs by TGF-ß in human lung cancer cells.

BACKGROUND: Transforming growth factor beta (TGF-ß) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-ß and a TGF-ß inhibitor, Galunisertib (LY2157299). RESULTS: TGF-ß reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-ß on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-ß, it was thought that TGF-ß induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-ß or Galunisertib. CONCLUSIONS: Therefore, inhibition of TGF-ß might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

Optimal placement of the region of interest for bolus tracking on brain computed tomography angiography in Beagle dogs.

This study aimed to determine the optimal placement of the region of interest (ROI) among four anatomical sites-pulmonary artery (PA), pulmonary vein (PV), aortic arch (AA), and carotid artery (CA)-in computed tomography (CT) brain angiography with automatic bolus tracking in healthy beagle dogs. Six beagles were included, and CT brain angiography was performed four times for each dog, to cover each ROI. The scan parameters, amount, and injection rate of the contrast medium were the same. The major intracranial arteries were selected for quantitative and qualitative evaluation: caudal cerebellar artery (CcA), basilar artery (BA), rostral cerebellar artery (RcA), caudal cerebral artery (CCA), middle cerebral artery (MCA), and rostral cerebral artery (RCA). Quantitative evaluation showed significantly higher CT attenuation values for the RcA, CCA, and MCA in the PA group and RcA and MCA in the PV group than in the CA group. Qualitative analysis revealed significantly higher scores for the BA, CCA, and MCA in the PA and PV groups than in the CA group. Venous contamination did not differ significantly among the ROIs, but the mean scores of the AA and CA groups were higher than those of the PA and PV groups. CT brain angiography using bolus tracking in the beagle dogs showed that the ROI should be placed at the PA or PV rather than at the CA for optimal images with strong contrast enhancement of the BA, RcA, CCA, and MCA and minimal venous contamination.

An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells.

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.