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Abstract Kawasaki disease (KD) causes vascular injury and lifelong remodeling. Excessive intimal proliferation has been observed, resulting in coronary artery lesions (CALs). However, the mechanisms underlying vascular remodeling in CAL and statin treatment have not been comprehensively elucidated. This study aimed to investigate the effects of statins on vascular remodeling using a KD mouse model. Candida albicans water‐soluble substance (CAWS) was intraperitoneally injected in 5‐week‐old male apolipoprotein‐E‐deficient mice. They were categorized as follows (n = 4): control, CAWS, CAWS+statin, and late‐statin groups. The mice were euthanized at 6 or 10 weeks after injection. Statins (atorvastatin) were initiated after CAWS injection, except for the late‐statin group, for which statins were internally administered 6 weeks after injection. Elastica van Gieson staining and immunostaining were performed for evaluation. Statins substantially suppressed the marked neointimal hyperplasia induced by CAWS. Additionally, CAWS induced TGFβ receptor II and MAC‐2 expression around the coronary arteries, which was suppressed by the statins. KD‐like vasculitis might promote the formation of aneurysm by destroying elastic laminae and inducing vascular stenosis by neointimal proliferation. The anti‐inflammatory effects of statins might inhibit neointimal proliferation. Therefore, statin therapy might be effective in adult patients with KD with CAL by inhibiting vascular remodeling.

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial flow reserve (MFR), and myocardial blood flow volume fraction (MBF) and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 men, 1 woman) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86 ± 0.13 vs. 1.08 ± 0.09, p = 0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23 ± 0.23 vs. 1.88 ± 0.29, p = 0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

Like humans, marmoset caregivers exhibit individual parenting styles. Among these, infant tolerance is in part regulated by a subregion of the medial preoptic area enriched with calcitonin receptor-expressing neurons.

Abstract Emerging evidence suggests that the mesolimbic dopaminergic network plays a role in the modulation of pain. As chronic pain conditions are associated with hypodopaminergic tone in the nucleus accumbens (NAc), we evaluated the effects of increasing signaling at dopamine D1/D2-expressing neurons in the NAc neurons in a model of neuropathic pain induced by partial ligation of sciatic nerve. Bilateral microinjection of either the selective D1-receptor (Gs-coupled) agonist Chloro-APB or the selective D2-receptor (Gi-coupled) agonist quinpirole into the NAc partially reversed nerve injury-induced thermal allodynia. Either optical stimulation of D1-receptor-expressing neurons or optical suppression of D2-receptor-expressing neurons in both the inner and outer substructures of the NAc also transiently, but significantly, restored nerve injury-induced allodynia. Under neuropathic pain-like condition, specific facilitation of terminals of D1-receptor-expressing NAc neurons projecting to the VTA revealed a feedforward-like antinociceptive circuit. Additionally, functional suppression of cholinergic interneurons that negatively and positively control the activity of D1- and D2-receptor-expressing neurons, respectively, also transiently elicited anti-allodynic effects in nerve injured animals. These findings suggest that comprehensive activation of D1-receptor-expressing neurons and integrated suppression of D2-receptor-expressing neurons in the NAc may lead to a significant relief of neuropathic pain.

Abstract trans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.

Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE−) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.

Multifunctional polyurethane shape memory polymers (PU-SMPs) have been of increasing interest in various applications. Here we report structure characterization, detailed methodology, and obtained results on the identification of functional properties of a thermoset PU-SMP (MP4510) with glass transition temperature of 45 °C. The stable, chemically crosslinked network of this thermoset PU-SMP results in excellent shape memory behavior. Moreover, the proximity of the activation temperature range of this smart polymer to room and body temperature enables the PU-SMP to be used in more critical industrial applications, namely fast-response actuators. The thermomechanical behavior of a shape memory polymer determines the engineering applications of the material. Therefore, investigation of the shape memory behavior of this class of commercial PU-SMP is of particular importance. The conducted structural characterization confirms its shape memory properties. The shape fixity and shape recovery properties were determined by a modified experimental approach, considering the polymer’s sensitivity to external conditions, i.e., the temperature and humidity variations. Three thermomechanical cycles were considered and the methodology used is described in detail. The obtained shape fixity ratio of the PU-SMP was approximately 98% and did not change significantly in the subsequent cycles of the thermomechanical loading due to the stability of chemical crosslinks in the thermoset materials structure. The shape recovery was found to be approximately 90% in the first cycle and reached a value higher than 99% in the third cycle. The results confirm the effect of the thermomechanical training on the improvement of the PU-SMP shape recovery after the first thermomechanical cycle as well as the effect of thermoset material stability on the repeatability of the shape memory parameters quantities.

Kawasaki disease (KD) is an acute form of systemic vasculitis that may promote atherosclerosis in adulthood. This study examined the relationships between KD, atherosclerosis, and the long-term effects of HMG-CoA inhibitors (statins). Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally into 5-week-old male apolipoprotein-E-deficient (Apo E-/-) mice to create KD-like vasculitis. Mice were divided into 4 groups: the control, CAWS, CAWS+statin, and late-statin groups. They were sacrificed at 6 or 10 weeks after injection. Statin was started after CAWS injection in all groups except the late-statin group, which was administered statin internally 6 weeks after injection. Lipid plaque lesions on the aorta were evaluated with Oil Red O. The aortic root and abdominal aorta were evaluated with hematoxylin and eosin staining and immunostaining. CAWS vasculitis significantly enhanced aortic atherosclerosis and inflammatory cell invasion into the aortic root and abdominal aorta. Statins significantly inhibited atherosclerosis and inflammatory cell invasion, including macrophages. CAWS vasculitis, a KD-like vasculitis, promoted atherosclerosis in Apo E-/- mice. The long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Therefore, statin treatment may be used for the secondary prevention of cardiovascular events during the chronic phase of KD.

The halogen bond has been widely used as an important supramolecular tool in various research areas. However, there are relatively few studies on halogen bonding related to molecular chirality. 3-(2-Halophenyl)quinazoline-4-thione derivatives have stable atropisomeric structures due to the rotational restriction around an N-C single bond. In X-ray single crystal structures of the racemic and optically pure N-C axially chiral quinazoline-4-thiones, we found that different types of intermolecular halogen bonds (C=S⋯X) are formed. That is, in the racemic crystals, the intermolecular halogen bond between the ortho-halogen atom and sulfur atom was found to be oriented in a periplanar conformation toward the thiocarbonyl plane, leading to a syndiotactic zig-zag array. On the other hand, the halogen bond in the enantiomerically pure crystals was oriented orthogonally toward the thiocarbonyl plane, resulting in the formation of a homochiral dimer. These results indicate that the corresponding racemic and optically pure forms in chiral molecules are expected to display different halogen bonding properties, respectively, and should be separately studied as different chemical entities.

To investigate the brain's response to music, many researchers have examined cortical entrainment in relation to periodic tunes, periodic beats, and music. Music familiarity is another factor that affects cortical entrainment, and electroencephalogram (EEG) studies have shown that stronger entrainment occurs while listening to unfamiliar music than while listening to familiar music. In the present study, we hypothesized that not only the level of familiarity but also the level of attention affects the level of entrainment. We simultaneously presented music and a silent movie to participants and we recorded an EEG while participants paid attention to either the music or the movie in order to investigate whether cortical entrainment is related to attention and music familiarity. The average cross-correlation function across channels, trials, and participants exhibited a pronounced positive peak at time lags around 130 ms and a negative peak at time lags around 260 ms. The statistical analysis of the two peaks revealed that the level of attention did not affect the level of entrainment, and, moreover, that in both the auditory-active and visual-active conditions, the entrainment level is stronger when listening to unfamiliar music than when listening to familiar music. This may indicate that the familiarity with music affects cortical activities when attention is not fully devoted to listening to music.

The transformation-induced stress relaxation and stress recovery of TiNi shape memory alloy (SMA) in stress-controlled subloop loading were investigated based on the local variation in temperature and transformation band on the surface of the tape in the tension test. The results obtained are summarized as follows. (1) In the loading process, temperature increases due to the exothermic martensitic transformation (MT) until the holding strain and thereafter temperature decreases while holding the strain constant, resulting in stress relaxation due to the MT; (2) In the unloading process, temperature decreases due to the endothermic reverse transformation until the holding strain and thereafter temperature increases while holding the strain constant, resulting in stress recovery due to the reverse transformation; (3) Stress varies markedly in the initial stage followed by gradual change while holding the strain constant; (4) If the stress rate is high until the holding strain in the loading and unloading processes, both stress relaxation and stress recovery are large; (5) It is important to take into account this behavior in the design of SMA elements, since the force of SMA elements varies even if the atmospheric temperature is kept constant.

(1) The paper presents experimental and numerical results of the TiNi shape memory alloy (SMA) subjected to a modified program of force-controlled tensile loading. The time-dependent development of transformation strain under the constant-force conditions was investigated to describe transformation-induced creep phenomena. (2) Mechanical characteristics of the TiNi SMA were derived using a testing machine, whereas the SMA temperature changes accompanying its deformation were obtained in a contactless manner with an infrared camera. A 3D coupled thermo-mechanical numerical analysis, realized in a partitioned approach, was applied to describe the SMA mechanical and thermal responses. (3) The stress and related temperature changes demonstrated how the transformation-induced creep process started and evolved at various stages of the SMA loading. The proposed model reproduced the stress, strain and temperature changes obtained during the experiment well; the latent heat production is in correlation with the amount of the martensitic volume fraction. (4) It was demonstrated how the transformation-induced creep process occurring in the SMA under such conditions was involved in thermo-mechanical couplings and the related temperature changes.

If the shape memory polymer is applied to actuators, the novel intelligent shape memory actuators can be developed. The development of the functionally-graded shape memory polymer board was investigated for the development of the new actuators. The results obtained are summarized as follows. (1) Based on the shape recovery and recovery stress, the temperature-dependent multistep actuation can be obtained by using the shape memory polymer sheets and foams with various glass transition temperatures in the shape memory polymer actuators. (2) The functionally-graded shape memory polymer board composed of shape memory polymer sheets and foams, showing the similar indentation deformation property as a finger, can be applied to the elements coming into contact with body in the nursing-care robots or actuators.

The transformation-induced stress relaxation and stress recovery of TiNi shape memory alloy (SMA) in the stress-controlled subloop loading were investigated based on the local variation in temperature and transformation band on the surface of the SMA tape in the tension test. The results obtained are summarized as bellows. (1) In the loading process, temperature increases due to the exothermic martensitic transformation (MT) till the holding strain under a constant stress rate and thereafter temperature decreases during holding the strain constant, resulting in stress relaxation due to the MT. (2) In the unloading process, temperature decreases due to the endothermic reverse transformation till the holding strain under a constant stress rate and thereafter temperature increases during holding the strain constant, resulting in stress recovery due to the reverse transformation. (3) Stress varies markedly in the initial stage followed by gradual change during holding the strain constant. (4) If stress rate is high till the holding strain in the loading and unloading processes, both stress relaxation and stress recovery are large. (5) It is important to take account of these behaviors in the design of SMA elements since the force of SMA elements can vary under constant strain even if temperature is kept constant around SMA elements.

The domestic chicken is an attractive model system to explore the development and function of brain circuits. Electroporation-mediated and retrovirus (including lentivirus) vector-mediated gene transfer techniques have been widely used to introduce genetic material into chicken cells. However, it is still challenging to efficiently transduce chicken postmitotic neurons without harming the cells. To overcome this problem, we searched for a virus vector suitable for gene transfer into chicken neurons, and report here a novel recombinant virus vector derived from avian adeno-associated virus (A3V). A3V vector efficiently transduces neuronal cells, but not non-neuronal cells in the brain. A single A3V injection into a postembryonic chick brain allows gene expression selectively in neuronal cells within 24 hrs. Such rapid and neuron-specific gene transduction raises the possibility that A3V vector can be utilized for studies of memory formation in filial imprinting, which occurs during the early postnatal days. A3V injection into the neural tube near the ear vesicle at early embryonic stage resulted in persistent and robust gene expression until E20.5 in the auditory brainstem. We further devised an A3V-mediated tetracycline (Tet) dependent gene expression system as a tool for studying the auditory circuit, consisting of the nucleus magnocellularis (NM) and nucleus laminaris (NL), that primarily computes interaural time differences (ITDs). Using this Tet system, we can transduce NM neurons without affecting NL neurons. Thus, the A3V technology complements current gene transfer techniques in chicken studies and will contribute to better understanding of the functional organization of neural circuits.

The superficial layer of the superior colliculus (sSC) receives visual inputs via two different pathways: from the retina and the primary visual cortex. However, the functional significance of each input for the operation of the sSC circuit remains to be identified. As a first step toward understanding the functional role of each of these inputs, we developed an optogenetic method to specifically suppress the synaptic transmission in the retino-tectal pathway. We introduced enhanced halorhodopsin (eNpHR), a yellow light-sensitive, membrane-targeting chloride pump, into mouse retinal ganglion cells (RGCs) by intravitreously injecting an adeno-associated virus serotype-2 vector carrying the CMV-eNpHR-EYFP construct. Several weeks after the injection, whole-cell recordings made from sSC neurons in slice preparations revealed that yellow laser illumination of the eNpHR-expressing retino-tectal axons, putatively synapsing onto the recorded cells, effectively inhibited EPSCs evoked by electrical stimulation of the optic nerve layer. We also showed that sSC spike activities elicited by visual stimulation were significantly reduced by laser illumination of the sSC in anesthetized mice. These results indicate that photo-activation of eNpHR expressed in RGC axons enables selective blockade of retino-tectal synaptic transmission. The method established here can most likely be applied to a variety of brain regions for studying the function of individual inputs to these regions.

The author aimed to enhance the functional characteristics of the proposed Ti–Ni shape memory alloy (SMA) with a functionally graded property by ultrasonic shot peening (USP) treatment. To the author’s knowledge, this was the first study in which USP treatment was utilized for manufacturing functionally graded SMAs; previous studies relied on powder metallurgy and hot rolling techniques. By examining the various properties of the specimens, the author confirmed the effects of hot rolling and USP treatment. Hot rolling and USP treatment led to an increased Vickers hardness. Hot rolling primarily contributed to densification, while USP treatment induced work hardening, resulting in increased hardness. The surface of TiNi SMA sintered bodies experienced compressive residual stress up to 300 MPa because of the USP treatment. The transformation peaks in differential scanning calorimetry curves shifted toward lower temperatures as the Ni content increased. Therefore, the transformation properties of the functionally graded shape memory alloys were unaffected by the USP treatment. The USP treatment work-hardens the sintered TiNi SMA produced through hot rolling. The effect was more pronounced in the high-Ni-concentration region, resulting in the development of a functionally graded behavior of deformation resistance. [ABSTRACT FROM AUTHOR]