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A transient model of frost growth on a flat plate was developed, taking the surface characteristics of the plate into consideration. Five regression models were applied, three traditional (Multiple Linear, LASSO, Ridge) and two machine-learning (Artificial Neural Network, Support Vector Machine) regression models. The training database was established using data extracted from previously published experimental studies. The experimental data consisted of forced convection (1067 data points) and natural convection data (992 data points). The model outputs were then evaluated using common statistical indicators and the best performing model was selected. The highest R2 values for the artificial neural network were 0.9899 and 0.9944 for forced and natural convection, respectively, after removal of outliers. The frost thickness was predicted for various conditions, including different surface characteristics. The model produced good predictions despite the occurrence of nonlinear complex growth mechanism dependent on various conditions in the dataset obtained.

We conducted numerical simulations to investigate the influence of the horizontal fin arrangement on the thermal performance of a phase change material (PCM)-filled heat sink. Six horizontal fin positions were considered to compare and analyze heat transfer features and variations in the base temperature of the heat sink. The enthalpy–porosity method was used to investigate the phase change process of the PCM and the interface between the PCM and air. The working fluid inside the heat sink was tracked using a volume of fluid model. Heat transfer phenomena during the solid PCM–melting process were examined. The time required to reach the set point temperature (SPT) and storage ratio have been reported for all fin configurations. When the horizontal fins were aligned at the center of the heat sink, the time taken to attain the lowest SPT was the longest and the storage ratio was the highest. In the presence of horizontal fins, the energy storage rate was improved by 3.8 % compared to the case without horizontal fins. In addition, a difference of 2.7 % energy storage ratio appeared depending on the arrangement of horizontal fins, revealing that there exists an arrangement of horizontal fins to effectively store the thermal energy input to the heat sink. The results herein can benefit the thermal management of heat sinks encountered when cooling electronics.

The measurement of absolute acoustic nonlinearity parameters using piezoelectric transducers consists of two steps; calibration and harmonic detection. In calibration, a frequency domain transfer function that converts the current output signal amplitude into the acoustic displacement amplitude is measured. Then, in harmonic detection, the amplitudes of the harmonics generated in the ultrasonic waves propagating through a medium are detected and converted to displacement amplitudes using the transfer function obtained in the calibration step for calculation of the acoustic nonlinearity parameters. However, in the conventional method, a broadband pulse signal is used for the calibration and a narrowband tone-burst signal is used for the harmonic detection; therefore, this method inconveniently uses different driving devices for calibration and harmonic detection. In this study, we propose a more convenient technique that can perform calibration using a narrowband signal so that a single driver of a narrowband signal can be used for both calibration and harmonic detection. To verify the validity of the proposed method, transfer functions were measured at typical frequencies for two types of material (aluminum alloy and fused silica) against two types of transducers (commercial PZT and LiNbO3 crystal), and the results were compared with those obtained using conventional calibration method. The transfer functions obtained by the conventional method and the proposed method showed good concordance, independent of material and transducer type.

Our objective was to analyze functional outcomes and prognostic factors in patients suffering from angiogram-negative non-perimesencephalic subarachnoid hemorrhage (non-PMH). In total, 1601 patients presenting with spontaneous SAH between January 2009 to December 2019 admitted to our institution were reviewed. Among them, 51 patients with angiogram negative non-perimesencephalic subarachnoid hemorrhage were analyzed. We divided patients into groups according to hemorrhage pattern and duration. Prognostic factors were assessed according to initial neurologic grade, early hydrocephalus, fisher grade, and duration of hemorrhage. Outcomes were assessed according to the modified Rankin Scale after 6 months. Overall, 41 patients (80.3%) with angiogram-negative non-PMH achieved a favorable outcome. In univariate analysis, good initial neurologic grade, absence of early hydrocephalus, non-Fisher-type 3 bleeding pattern, and short term hemorrhage (blood wash out7 days after onset) duration were significantly associated with a favorable outcome. In multivariate analysis, a non-Fisher-type 3 hemorrhagic pattern (p 0.05) and good initial neurologic state (p 0.01) were independent predictors of favorable outcomes in angiogram-negative non-PMH patients. Patients with angiogram-negative non-PMH generally had favorable outcomes. A non-Fisher-type 3 hemorrhagic pattern and good initial neurologic state were prognostic factors of a favorable outcome in non-PMH. Furthermore, patients with long-term SAH were more likely to develop hydrocephalus. Evaluating the pattern and duration of subarachnoid hemorrhage may allow better prediction of outcomes in patients with angiogram negative and non-PMH.

In gamma knife radiosurgery, the tumor response to radiation is an important predictor of clinical treatment results. Since brain tumors have different characteristics and growth patterns, depending on the type, the tumors' response to radiation are also different. Compared with various other clinical treatments, there is a dearth of research on the development of gamma knife-magnetic resonance imaging (MRI) preclinical experimental equipment. Hence, the identification of preclinical equipment necessity for experimental animals will provide meaningful data for the provision of clinical assistance to humans.A device for stereotactic radiosurgery capable of MRI in small animals was developed. The feasibility of creating a preplan by means of small animal images was then assessed.A device for stereotaxic surgery of small animals using a 48-channel MRI coil was developed using a 3 dimensional printer. Rat brain-MRI images were obtained with a 3.0 T MRI scanner using a multi-channel coil. The acquired MRI images were transferred to a GammaPlan workstation to establish a preplan.To gamma rays to the targeted site on animals, a positioning device combined with a G-frame was mounted on a gamma knife. Planning of radiosurgery based on MRI images became possible with GammaPlan workstations.Preclinical experiments using small animals are possible with the use of stereotactic devices. In clinical treatment, preclinical experimental results will provide meaningful information.

Directed energy deposition (DED) is an additive manufacturing technique wherein a focused thermal energy source and a coaxial powder delivery system are combined for the fabrication of metallic parts. Although rapid progress has been made in DED, the amount of research performed for in situ quality monitoring during fabrication is limited. Grain size monitoring during DED is particularly important because the grain size is directly related to the mechanical strength and stiffness of the final products. In this study, a layer-by-layer grain size estimation technique using femtosecond laser ultrasonics is developed for in situ monitoring during DED. The proposed technique employs fully noncontact and nondestructive testing for grain size estimation and uses the relationship between the laser-induced ultrasonic waves and the grain size. In addition to the in situ operation of the technique, spatial resolution in the micrometer range was achieved. The developed technique was validated using Ti-6Al-4V specimens fabricated by DED. The results of the quantitative grain sizes measured by the developed method were consistent with those measured through independent metallography conducted after the completion of DED.

In our technology-driven world, various methods for teaching in an educational venue or in a simulated environment have been suggested especially for computer and coding education, among which virtual learning is a widely used teaching approach. In particular, IoT (Internet of Things)-related education has been made possible owing to the industrial developments that have occurred in various fields since the Fourth Industrial Revolution. Because it is mostly based on hardware and simple operations taught in a two-dimensional (2D) environment, conventional virtual learning of coding decreases the interest among learners. Therefore, there is a need for a three-dimensional (3D)-based educational approach that can arouse interest in learners. The proposed model allows various IoT systems to be indirectly built; it provides an inexpensive learning method by applying a simulation system in a 3D environment. The model is implemented on IoT devices, real IoT systems, and an IoT simulator based on the Arduino platform, thereby reducing the cost of building an education system while at the same time arousing the interest of learners with its 3D environment for learning. Various education-related content can be provided to learners through such an indirectly developed system. A header file type library is created by analyzing the prototype of the GPIO (general-purpose input/output) function suitable for the IoT device to be used in the virtual IoT simulator; a virtual remote IO module is also implemented. In addition, the physical and electrical characteristics of the peripheral devices to be applied were identified and implemented in a virtual space. Sensors and actuators with various characteristics were implemented to enhance the educational effect, and a test code was written to check the consistency of an operation between the real system and the virtual system. An experiment conducted to check the update cycle of the actual input and output showed that they differ by more than 5,000 fold on average. This is a physical limitation resulting from the difference between a method that directly controls an actual electrical signal with a register and a method of transmitting and receiving signals through a communication device. The actual system motion analysis showed no cases in which the automatic guided vehicle (AGV) deviated from the line and there was a slight difference in the responsiveness when returning to the original position from the deviation.

This study proposed deep learning-based ultrasonic nondestructive testing for porosity evaluation of additively manufactured components. First, porosity mechanisms according to additive manufacturing (AM) processing conditions were studied using traditional scanning acoustic microscopy and optical microscopy. Second, correlations between ultrasonic properties and porosity content were analyzed. The correlation results showed that the increased porosity content resulted in a decreased ultrasonic velocity and increased ultrasonic attenuation coefficient. Third, various levels of porosities were evaluated using a deep learning model based on a fully connected deep neural network that was trained on raw ultrasonic signals measured in the AM samples. After training, the testing performance of the trained model was evaluated. Additionally, the generalization performance of the pre-trained model was assessed using newly fabricated AM samples that were not used for training. The results showed that the porosity content evaluated by the pre-trained model matched well with that measured via traditional scanning acoustic microscopy, thus demonstrating the feasibility of deep learning-based ultrasonic nondestructive testing for porosity evaluation of additively manufactured components.

This study was conducted to investigate the effectiveness of ultrasonic testing (UT) and eddy current testing (ECT) for the porosity evaluation of additive manufactured (AM) parts. AM samples containing different levels of porosity were fabricated at varying laser scanning speeds. The porosity of each sample was evaluated through scanning acoustic microscopy, which was adopted as reference. For UT, the ultrasonic velocity and ultrasonic attenuation coefficient were measured with an ultrasonic contact transducer using the traditional pulse-echo method. For ECT, the electrical conductivity was measured using an eddy current electrical conductivity meter. The relationship between the measured parameters and the porosity content showed that an increase in the porosity content decreased the ultrasonic velocity, increased the ultrasonic attenuation coefficient, and decreased the electrical conductivity. UT was preferred in terms of measurement sensitivity, whereas ECT facilitated a simple setup and high inspection speeds.

The present study investigated the unique contributions of relational spirituality and humility factors to seminary students’ eudaimonic well-being in a diverse sample ( n = 111) of urban seminary students. Hypotheses were developed in conversation with this research on humility, seminary student formation, and virtue ethics. As hypothesized, the relational spirituality factors of differentiation of self and quest exploration each made a significant independent contribution in predicting students’ well-being over and above impression management. In addition, humility-cultivating practices and dispositional humility were modestly correlated and each made a significant independent contribution in predicting well-being over and above relational spirituality factors and impression management. Implications for future research and for seminary student formation are discussed.

We report 2 cases of arrested pneumatization of the sphenoid sinus, a normal variant commonly misdiagnosed as a serious condition of the skull base. A 65-year-old man visited a local clinic for regular checkups. Brain CT showed a non-expansile lesion of the soft tissue with a well-defined sclerotic margin in the clivus but without destruction or mass effect on the surrounding bony structures. Subsequent brain MRI revealed that the lesion within the clivus was a high-signal lesion on the T2-weighted image, containing a low-signal round mass seen on a high-intensity signal on the T1-weighted image without contrast enhancement. Thus, the lesion was considered to contain internal fat. A 70-year-old woman diagnosed with a tumor in the greater sphenoid bone visited our hospital. Her brain CT revealed a non-expansile lesion of mixed density and a well-demarcated lesion and internal curvilinear calcification in the left greater wing of the sphenoid bone. The margin was osteosclerotic and the adjacent bony structure was intact. Her brain MRI showed that the lesion within the greater sphenoid bone had multiple low-signal lesions within a high-signal lesion on the T2-weighted image, suggesting internal fat contents. The lesions were diagnosed as arrested pneumatization of the sphenoid sinus and no further examination or treatment was performed. Arrested pneumatization of the sphenoid sinus should be considered in the presence of non-expansile lesion with an osteosclerotic boundary and internal fat component in the skull base.

Gene expression in HIV-1 is regulated by the promoters in 5' long-terminal repeat (LTR) element, which contain multiple DNA regulatory elements that serve as binding sites for cellular transcription factors. YY1 could repress HIV-1 gene expression and latent infection. Here, however, we observed that virus production can be increased by YY1 over-expression and decreased under YY1 depleted condition by siRNA treatment. To identify functional domain(s) of YY1 activation, we constructed a number of YY1 truncated mutants. Our data show that full-length YY1 enhances the viral transcription both through U3 and U3RU5 promoters. Moreover, the C-terminal region (296-414 residues) of YY1 is responsible for the transcriptional upregulation, which could be enhanced further in the presence of the viral Tat protein. The central domain of YY1 (155-295 residues) does not affect LTR activity but has a negative effect on HIV-1 gene expression. Taken together, our study shows that YY1 could act as a transcriptional activator in HIV-1 replication, at least in the early stages of infection. [BMB Reports 2020; 53(5): 248-253].

Objective We retrospectively evaluated the efficacy of Gamma Knife radiosurgery (GKS) for recurrent nasopharyngeal carcinoma (NPC) in patients who previously underwent radiotherapy, and analyzed the treatment outcomes over 14 years. Methods Ten patients with recurrent NPC who had previously received radiotherapy underwent stereotactic radiosurgery using a Gamma Knife® (Elekta Inc, Atlanta, GA, USA) between 2005 and 2018. The median target volume was 8.2 cm3 (range, 1.7-17.8), and the median radiation dose to the target was 18 Gy (range, 12-30). The median follow-up period was 18 months (range, 6-76 months). Overall and local failure-free survival rates were determined using the Kaplan-Meier method. Results The NPCs recurred at the primary cancer site in seven patients (70%), as distant brain metastasis in two (20%), and as an extension into brain in one (10%). The recurrent tumors in seven of the 10 patients (70%) were found on the routine follow-up imaging studies. Two patients presented with headache and one with facial pain. Local failure after GKS occurred in five patients (50%) : two of whom died eight and 6 months after GKS, respectively. No adverse radiation effects were noted after GKS. The 1- and 3-year overall survival rates after GKS were 90% and 77%, respectively. The local failure-free survival rates at 6 months, 1 year, and 3 years after GKS were 80%, 48%, and 32%, respectively. The median interval from GKS to local failure was 8 months (range, 6-12). Univariate analysis revealed that using co-registration with positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) was associated with a lower local failure rate of recurrent NPC (p=0.027). Conclusion GKS is an acceptable salvage treatment option for patients with recurrent NPC who previously received radiation therapy. PET-CT and MRI co-registration for dose planning can help achieve local control of recurrent NPC.

Sinonasal teratocarcinosarcoma (SNTCS), a very rare tumor, is known to be a heterogeneous with epithelial, mesenchymal, and neuroepithelial components and shows a very aggressive clinical course. Due to the heterogeneity of this tumor, it is often misdiagnosed. No definitive treatment modality has been reported because it is a very rare tumor. A 44-year-old man presented to a rhinologist with headache and nasal obstruction, and an intranasal tumor was found that invaded into the cranial cavity. He underwent combined surgery with a rhinologist and a neurosurgeon following cognitive decline that worsened after a transnasal biopsy. The patient was diagnosed with SNTCS and underwent radiotherapy. However, residual tumor was found during radiotherapy and additional chemotherapy was administered. Follow-up brain MRI revealed no remnant or recurrent lesion. SNTCS is a tumor that has not yet been well researched and should be further investigated for proper treatment.

Primary central nervous system vasculitis (PCNSV) is rare, and the diagnosis is difficult to make because of its variable radiologic expressions. Early corticosteroid therapy often is effective. Herein we report the case of a 56-year-old man who had a well-enhanced cystic mass with severe edema in the right frontal lobe, which was initially felt to be a malignancy. Histologic examination of tissue removed at craniotomy revealed that it was a PCNSV. Despite early administration of corticosteroids, a new lesion developed within 3 days. The lesions responded to treatment with cyclophosphamide and corticosteroid.

Theoretical and numerical studies were conducted to investigate the transitional interpillar spacing for dual-scale structures, where wetting transition between the Wenzel and Cassie-Baxter states occurs in the primary and secondary pillars. A theoretical formula was derived for the transitional interpillar spacing based on the continuum picture of water. Molecular dynamics (MD) simulations were carried out by varying the interpillar spacing for the primary pillars for single- and dual-scale structures with various pillar heights. The results obtained from the theoretical formula agreed reasonably well with the results obtained from MD simulations, especially when the primary pillar height was relatively high. The transitional interpillar spacing increases as the pillar height and the number of secondary pillars increase. The effect of the secondary pillars on the transitional interpillar spacing was also evaluated using the difference in the grand potentials between the Wenzel and Cassie-Baxter states. These results show that the dual-scale structures increase the transitional interpillar spacing with an increase in the surface hydrophobicity.

The transversus abdominis plane (TAP) block is an ideal pain control method used in surgeries that require abdominal wall incisions through the injection of an anesthetic solution into the plane between the internal oblique muscle and transversus abdominis muscle. Herein, we report an 83-year-old man who was diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and underwent lumboperitoneal shunt surgery (LPS). The TAP block was performed before LPS, and the numerical rating scale for pain was 0 at day 1 after the surgery. The patient was discharged early at day 3 after surgery despite the patient being extremely old, as he reported quick relief from the postoperative abdominal pain. The TAP block can hence be considered for use before LPS in elderly patients with iNPH.

Recently, we showed that synthetic anion transporters DSC4P-1 and SA-3 had activity related to cancer cell death. They were found to increase intracellular chloride and sodium ion concentrations. They were also found to induce apoptosis (DSC4P-1) and both induce apoptosis and inhibit autophagy (SA-3). However, determinants underlying these phenomenological findings were not elucidated. The absence of mechanistic understanding has limited the development of yet-improved systems. Here, we show that three synthetic anion transporters, DSC4P-1, SA-3, and 8FC4P, induce osmotic stress in cells by increasing intracellular ion concentrations. This triggers the generation of reactive oxygen species via a sequential process and promotes caspase-dependent apoptosis. In addition, two of the transporters, SA-3 and 8FC4P, induce autophagy by increasing the cytosolic calcium ion concentration promoted by osmotic stress. However, they eventually inhibit the autophagy process as a result of their ability to disrupt lysosome function through a transporter-mediated decrease in a lysosomal chloride ion concentration and an increase in the lysosomal pH.

Delta neutrophil index (DNI), which reflects the fraction of immature granulocytes, is used to detect infection and sepsis from noninfectious conditions, but few studies have evaluated in the early stage of acute poisoning. This retrospective observational study was performed on acute poisoning patients who visited to the emergency department (ED) and were consecutively admitted in intensive care units over 18-month period. The serial DNI, conventional inflammatory biomarkers, and culture results were obtained in the ED and after admission. The outcomes were the identification of sepsis, bacteremia, and 30-day mortality. Of 166 patients (mean age, 56.0 years) in this cohort, 59 (35.5%) had sepsis and 29 (17.5%) had bacteremia. Initial and peak DNI fractions 24 h after ED admission were strong independent predictors of sepsis development. Analysis of the area under the curve according to multiple receiver operating characteristics showed that DNI had a higher capability to predict sepsis than other parameters (0.815 for DNI, 0.700 for procalcitonin, 0.681 for C-reactive protein, and 0.741 for white blood cell). Using multivariable logistic regression analysis, it was found that DNI was an independent predictor of sepsis (95% confidence interval (CI) of odds: 1.03–1.18) and bacteremia (95% CI: 1.01–1.14). Therefore, initial and serial measurement of DNI may serve as useful risk predictor for development of sepsis or bacteremia in acute poisoning.

Herein we report the first small molecule that disrupts the survivin-Smac interaction taking place in mitochondria. The inhibitor, PZ-6-QN, was identified by initially screening a phenothiazine library using a fluorescence anisotropy assay and then conducting a structure-activity relationship study. Mutagenesis and molecular docking studies suggest that PZ-6-QN binds to survivin similarly to the known Smac peptide, AVPI. The results of the effort also show that PZ-6-QN exhibits good anticancer activity against various cancer cells. Moreover, cell-based mechanistic studies provide evidence for the proposal that PZ-6-QN enters mitochondria to inhibit the survivin-Smac interaction and promotes release of Smac and cytochrome c from mitochondria into the cytosol, a process that induces apoptosis in cancer cells. Overall, the present study suggests that PZ-6-QN can serve as a novel chemical probe for study of processes associated with the mitochondrial survivin-Smac interaction and it will aid the discovery of novel anticancer agents.

Objective The aim of this study was to analyze serum levels of vascular endothelial growth factor (VEGF) and endostatin in patients with cerebral treated by stereotactic radiosurgery (SRS), and to assess their association with radiological radiation-induced changes (RICs). Methods To measure serum biomarkers, peripheral venous blood was collected before SRS and 1 week, 1 month, 3 months, and 6 months after SRS. To evaluate RICs, clinical and neuroimaging follow-up were performed concurrently every 6 months after SRS. Results Twenty-seven patients were enrolled (11 in the group with RIC, 16 in the group without RIC). Serum VEGF and endostatin levels were positively correlated (P = 0.036, r = 0.405). In the group with RIC, the median serum VEGF 6 months after SRS (58.98 pg/mL) was significantly higher than that of the group without RIC (15.17 pg/mL) (P = 0.001). Multivariate analysis revealed that higher VEGF 6 months after SRS (P = 0.001, hazard ratio, 1.032; 95% confidence interval, 1.012–1.052) and lower endostatin 1 month after SRS (P = 0.007, hazard ratio, 0.964; 95% confidence interval, 0.935–0.993) were significantly associated with RICs. Conclusions Our results show that serum levels of VEGF 6 months after SRS were higher in the group with RIC. Serum levels of VEGF 6 months and endostatin 1 month after SRS were associated with the radiological RICs. Thus, serial measurements of serum VEGF and endostatin after SRS might help predict RICs in patients with arteriovenous malformation treated by SRS.

An hydroxythiophene-conjugated benzothiazole (T2(OH)B) was synthesized as a pH sensitive fluorescent probe. T2(OH)B displayed dual emission behavior due to the excited state intramolecular proton transfer (ESIPT) process, while the methoxy analogs, T2(OMe)B, did not. T2(OH)B showed strong fluorescence enhancement above physiological pHs. The applicability of T2(OH)B as a biological pH indicator was demonstrated by its use for staining mitochondrial compartment and H. pylori. Owing to its strong fluorescence emission with a large stokes shift and its effective response to pH, T2(OH)B serves as a platform for the design of new types of fluorescent probes.

We report two rare cases of spontaneously regressed Rathke's cleft cyst (RCC). A 52-year-old woman presented with headache. A pituitary hormone study was normal. Brain magnetic resonance imaging (MRI) showed a 0.45-cm3 cystic sellar lesion. The cyst was hyperintense on T1-weighed imaging and hypointense on T2-weighted imaging without rim enhancement, comparable to a RCC. Six months later, brain MRI showed no change in the cyst size. Without any medical treatments, brain MRI 1 year later revealed a spontaneous decrease in cyst volume to 0.05 cm3. A 34-year-old woman presented with headache and galactorrhea lasting 1 week. At the time of the visit, the patient's headache had disappeared. Her initial serum prolactin level was 81.1 ng/mL, and after 1 week without the cold medicine, the serum prolactin level normalized to 11.28 ng/mL. Brain MRI showed a RCC measuring 0.71 cm3. Without further treatments, brain computed tomography 6 months later showed a spontaneous decrease in cyst volume to 0.07 cm3. Another 6 months later, brain MRI revealed that the cyst had remained the same size. Neither patient experienced neurological symptoms, such as headache or visual disturbance, during the period of cyst reduction. The RCCs in both patients underwent spontaneous regression without any medical treatment during a period of 6 months to 1 year. Although spontaneous regression of a RCC is rare, it is still possible and a sufficient follow-up period should be considered.

Background The natural compound curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of curcumin via suppression of fascin expression in GBM cells. Methods U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence. Results At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10 μM/L curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells. Conclusion Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.

Hsp70 is known to directly bind to Bax for suppression of apoptosis. However, mechanisms on how Bax is dissociated from its complex with Hsp70 during apoptosis remain largely unknown. In the current study, we developed the efficient fluorescence resonance energy transfer (FRET) system which consisted of Hsp70-YFP and fluorescent amino acid (ANAP)-incorporated Bax, which was generated by using genetic code expansion technology, and applied the FRET system to elucidate mechanisms on how apoptosis-inducing substances dissociate Bax from Hsp70. Time-dependent analysis of single live cell images showed that Bax activators binding to Bax trigger sites inhibited the Bax-Hsp70 interaction but a Bax activator, which blocks phosphorylation of S184 via binding to the C-terminal S184 site, did not affect this interaction. Additionally, an inhibitor for Hsp70-Hsp40 interaction blocked the Bax-Hsp70 interaction. Furthermore, p53 activators promoted the dissociation of Bax from Hsp70 by reactivating p53 which disrupted the Bax-Hsp70 interaction. We also found that death ligands and a Bcl-2 inhibitor enhanced the dissociation of Bax from Hsp70 by activating activator BH3-only proteins. Results from this effort suggest that FRET systems consisting of the ANAP-incorporated protein and the YFP fusion protein will be valuable tools to gain an understanding of other types of protein-protein interactions.

Human pluripotent stem cell (hPSC)-derived myogenic progenitor cell (MPC) transplantation is a promising therapeutic approach for a variety of degenerative muscle disorders. Here, using an MPC-specific fluorescent reporter system (PAX7::GFP), we demonstrate that hPSC-derived MPCs can contribute to the regeneration of myofibers in mice following local injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal lamina of regenerated myofibers, adopt a quiescent state, and contribute to regeneration upon reinjury and in mdx mouse models. This subset of PAX7::GFP MPCs undergo a maturation process and remodel their molecular characteristics to resemble those of late-stage fetal MPCs/adult satellite cells following in vivo engraftment. These in-vivo-matured PAX7::GFP MPCs retain a cell-autonomous ability to regenerate and can repopulate in the niche of secondary recipient mice, providing a proof of principle for future hPSC-based cell therapy for muscle disorders.