Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells.

Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus, where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations. These results demonstrate that mitophagy controls the activities of p53 to maintain hepatic CSCs and provide an explanation as to why autophagy is required to promote hepatocarcinogenesis.

Effect of diabetes and corticosteroid injection on glenohumeral joint capsule in a rat stiffness model.

PURPOSE: To evaluate the effects of diabetes and corticosteroid injected in the joints on the shoulder motion, gait, and joint capsular properties in a rat stiffness model. METHODS: A total of 27 rats were randomly distributed into 3 groups-nondiabetes group (group A), diabetes group (group B), and diabetes plus steroid injection group (group C). The diabetes model was developed by inducing hyperglycemia with a submaximal dose of streptozotocin and the stiffness model by completely immobilizing the right shoulder of each animal in all groups with sutures passed between the scapula and humeral shaft. The left shoulder was used as an untreated control in all groups. Three weeks after immobilization, the sutures were removed in all groups, and a single dose of triamcinolone acetonide (0.5 mg/kg) was injected into the glenohumeral joint in group C. After 3 weeks of free activity, range of motion (ROM) evaluation, gait analysis by stride length, and capsular area measurement were performed in all rats. RESULTS: Hyperglycemia was successfully induced with a mean blood glucose level of 448.9±55.9 mg/dL in group B and 431.6±17.8 mg/dL in group C, which were significantly higher than 136.5±13.4 mg/dL in group A (P < .001). A significantly smaller ROM and stride length were found in the right (stiffness-induced) shoulder than that in the left (control) shoulder only in group B, and significantly larger capsular area in the right shoulder than that in the left shoulder in groups A and B (all P < .05). However, in group C, there were no differences between the right and left shoulders in all measurements (all P > .05). In case of the right shoulders in each group, group C showed significantly larger ROM (68° ± 11° vs. 42° ± 7°) and smaller capsular area (3934.4 ± 537.1 pixels vs. 7402.3 ± 1840.3 pixels) than group B (all P < .0167). CONCLUSIONS: The diabetic model had a detrimental effect on the development of stiffness by thickening the joint capsule, and an intra-articular steroid injection resolved the thickened joint capsule and restored shoulder motion.

Relationship between fatty infiltration and gene expression in patients with medium rotator cuff tear.

BACKGROUND: Fatty infiltration (FI) is a key prognostic factor that affects outcomes after rotator cuff repair and is radiologically evaluated using the Goutallier classification. The purpose of this study was to assess alterations in gene and protein expression according to the Goutallier classification in the supraspinatus muscle and any relationships among various gene expression profiles. METHODS: Twenty-four samples of the supraspinatus muscle from 12 patients with a high FI grade (grade 3 or 4) and 12 patients with a low FI grade (grade 1 or 2) with medium-sized tears were acquired during arthroscopic surgery. Alterations in the expression of genes and proteins associated with adipogenesis, fibrosis, inflammation, and muscle atrophy were compared between the high- and low-FI groups using reverse-transcription quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. RESULTS: mRNA expression of not only the adipogenic genes (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α; P < .001 and P = .020) but also the fibrosis-related gene (α-smooth muscle actin; P < .001), inflammation-related genes (interleukin [IL]-1ß and tumor necrosis factor α; P = .041 and P = .039), and muscle atrophy-related genes (atrogin 1 and myostatin; P = .006 and P < .001) was higher in the high-FI group compared with that in the low-FI group. In addition, adipogenic gene expression was significantly correlated with the expression of other categories of genes (all P < .05, except atrogin 1). A correlation of gene and protein expression was observed for IL-1ß (P = .027) and myostatin (P = .029). CONCLUSIONS: The radiologic grading of FI was associated with the expression of various genes, including adipogenic, fibrotic, inflammatory, and atrophy-related genes, and these genes were closely correlated with each other in terms of expression. This information could be helpful in patient counseling.

Development and validation of the fall risk perception questionnaire for patients in acute care hospitals.

AIMS AND OBJECTIVES: This study aimed to develop a fall risk perception questionnaire for patients admitted to acute care hospitals and to establish its reliability and validity. BACKGROUND: To prevent falls during patients' hospitalisation, it is essential for them to accurately perceive their risk of falling. DESIGN: This methodological study was performed to develop a fall risk perception questionnaire. METHODS: After generating a preliminary questionnaire, two rounds of content validity testing were performed with nine experts. Following a pilot test, a convenience sample of 236 participants was recruited from an acute care hospital between 2 May 2018 and 15 December 2019. Construct, convergent and known-group validity of the questionnaire was evaluated, and reliability was estimated by calculating the internal consistency reliability coefficients. The study adhered to STROBE guidelines. RESULTS: Exploratory factor analysis yielded a three-factor solution with 27 items. The questionnaire showed statistically significant positive correlation with the Korean Falls Efficacy Scale-International and the Morse Fall Scale, thus establishing convergent validity. For known-group comparison, Morse Fall Scale scores were categorised into two groups by cut-off score. The risk for falls group had a significantly higher perceived fall risk than the no risk for falls group, thus establishing known-group validity. Cronbach's alpha values indicated good to excellent reliability for the overall questionnaire with 27 items and for each of the three subfactors. CONCLUSIONS: The fall risk perception questionnaire demonstrated satisfactory reliability and validity in an acute care hospital setting. RELEVANCE TO CLINICAL PRACTICE: Because understanding patients' perceptions of their fall risk is essential for preventing falls, it is necessary to regularly assess patients' fall risk perception using tools with established reliability and validity.

Regulation of Apolipoprotein E Trafficking by Hepatitis C Virus-Induced Autophagy.

Apolipoprotein E (ApoE) plays an important role in the maturation and infectivity of hepatitis C virus (HCV). By analyzing the subcellular localization of ApoE in Huh7 hepatoma cells that harbored an HCV subgenomic RNA replicon, we found that ApoE colocalized with autophagosomes. This colocalization was marginally detected in HCV-infected cells, apparently due to the depletion of ApoE by HCV, as treatment with bafilomycin A1 (BafA1), a vacuolar ATPase inhibitor that inhibits autophagic protein degradation, partially restored the ApoE level and enhanced its colocalization with autophagosomes in HCV-infected cells. The role of HCV-induced autophagy in the degradation of ApoE was further supported by the observations that nutrient starvation, which induces autophagic protein degradation, led to the loss of ApoE in HCV subgenomic RNA replicon cells and that the knockdown of ATG7, a protein essential for the formation of autophagic vacuoles, increased the ApoE level in cells with productive HCV replication. Interestingly, the inhibition of autophagy by ATG7 knockdown reduced the colocalization of ApoE with the HCV E2 envelope protein and the HCV titers released from cells. In contrast, the treatment of cells with BafA1 enhanced the colocalization of ApoE and HCV E2 and increased both intracellular and extracellular HCV titers. These results indicated that autophagy played an important role in the trafficking of ApoE in HCV-infected cells. While it led to autophagic degradation of ApoE, it also promoted the interaction between ApoE and HCV E2 to enhance the production of infectious progeny viral particles.IMPORTANCE Hepatitis C virus (HCV) is one of the most important human pathogens. Its virion is associated with apolipoprotein E (ApoE), which enhances its infectivity. HCV induces autophagy to enhance its replication. In this report, we demonstrate that autophagy plays an important role in the trafficking of ApoE in HCV-infected cells. This leads to the degradation of ApoE by autophagy. However, if the autophagic protein degradation is inhibited, ApoE is stabilized and colocalized with autophagosomes. This leads to its enhanced colocalization with the HCV E2 envelope protein and increased production of infectious progeny viral particles. If autophagy is inhibited by suppressing the expression of ATG7, a gene essential for the formation of autophagosomes, the colocalization of ApoE with E2 is reduced, resulting in the reduction of progeny viral titers. These results indicate an important role of autophagy in the transport of ApoE to promote the production of infectious HCV particles.

HCV-induced autophagosomes are generated via homotypic fusion of phagophores that mediate HCV RNA replication.

Hepatitis C virus (HCV) induces autophagy to promote its replication, including its RNA replication, which can take place on double-membrane vesicles known as autophagosomes. However, how HCV induces the biogenesis of autophagosomes and how HCV RNA replication complex may be assembled on autophagosomes were largely unknown. During autophagy, crescent membrane structures known as phagophores first appear in the cytoplasm, which then progress to become autophagosomes. By conducting electron microscopy and in vitro membrane fusion assay, we found that phagophores induced by HCV underwent homotypic fusion to generate autophagosomes in a process dependent on the SNARE protein syntaxin 7 (STX7). Further analyses by live-cell imaging and fluorescence microscopy indicated that HCV-induced phagophores originated from the endoplasmic reticulum (ER). Interestingly, comparing with autophagy induced by nutrient starvation, the progression of phagophores to autophagosomes induced by HCV took significantly longer time, indicating fundamental differences in the biogenesis of autophagosomes induced by these two different stimuli. As the knockdown of STX7 to inhibit the formation of autophagosomes did not affect HCV RNA replication, and purified phagophores could mediate HCV RNA replication, the assembly of the HCV RNA replication complex on autophagosomes apparently took place during the formative stage of phagophores. These findings provided important information for understanding how HCV controlled and modified this important cellular pathway for its own replication.

Improvement in Light Extraction Efficiency of InGaN/GaN Blue Light Emitting Diodes Using Sidewall Texturing.

Herein, we reported the effects of the geometric morphology of the sidewall on the extraction efficiency of GaN-based light-emitting diodes (LEDs). We performed numerical analysis based on the ray-tracing method. We found that the extraction efficiency of the LEDs increased with the texturing of the sidewall. The light output intensity of the LEDs (at an injection current of 100 mA) increased by 13.8% after sidewall texturing. These results confirmed that the geometric morphology of the sidewall plays an important role in improving the extraction efficiency of LEDs.

Influence of Smoking on the Expression of Genes and Proteins Related to Fat Infiltration, Inflammation, and Fibrosis in the Rotator Cuff Muscles of Patients With Chronic Rotator Cuff Tears: A Pilot Study.

PURPOSE: To evaluate the altered gene and protein expression patterns in the rotator cuff muscles of smokers and non-smokers with rotator cuff tears and to identify the smoking-associated key genetic factor(s) involved in rotator cuff muscle physiology. METHODS: Twenty-four samples of rotator cuff muscle from 12 current heavy smokers (mean age 61.8 ± 5.1 years) and age- and sex-matched 12 non-smokers (mean age 61.8 ± 6.9 years) with medium-sized tears were acquired during arthroscopic surgery. As a statistical method, the propensity score matching technique was used to select control group by 1:1 matching for age and sex. Inclusion criteria were patients who underwent arthroscopic repair for medium-sized full-thickness rotator cuff tears and those that were current smokers with a smoking history >20 packs/year. Patients lacking medium-sized tears, those with recent steroid injection history, isolated subscapularis tear, preoperative stiff shoulder, acute traumatic tear, or previous surgery on the same shoulder, or those that declined to participate were excluded. Alterations in the expression of genes and proteins associated with myogenesis, inflammation, adipogenesis, and muscle fibrosis were compared between smokers and non-smokers with reverse-transcription quantitative polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: Histologic analysis revealed increased inflammation and remarkable fat accumulation and fibrogenesis in the rotator cuff muscle from smokers compared with that from non-smokers. The mRNA expression levels of inflammatory high mobility group box 1 (HMGB1; P = .043), adipogenic CCAAT/enhancer-binding protein alpha (P = .046) and peroxisome proliferator-activated receptor gamma (PPARγ; P = .048), myogenic differentiation 1 (P = .032), fibrogenic alpha-smooth muscle actin (α-SMA; P = .033), and metalloproteinase 9 (P = .036) were significantly greater in samples from smokers than from non-smokers. A correlation was observed between gene and protein expression of HMGB1 (P = .034), PPARγ (P = .021), and α-SMA (P = .021). CONCLUSIONS: Smokers with rotator cuff tears showed high inflammation, large fat infiltration, and fibrosis in rotator cuff muscle that is associated with the increased expression of HMGB1, PPARγ, and α-SMA, respectively. LEVEL OF EVIDENCE: Case control study (Prognostic level III).

Augmented Quantum Yield of a 2D Monolayer Photodetector by Surface Plasmon Coupling.

Monolayer (1L) transition metal dichalcogenides (TMDCs) are promising materials for nanoscale optoelectronic devices because of their direct band gap and wide absorption range (ultraviolet to infrared). However, 1L-TMDCs cannot be easily utilized for practical optoelectronic device applications (e.g., photodetectors, solar cells, and light-emitting diodes) because of their extremely low optical quantum yields (QYs). In this investigation, a high-gain 1L-MoS2 photodetector was successfully realized, based on the surface plasmon (SP) of the Ag nanowire (NW) network. Through systematic optical characterization of the hybrid structure consisting of a 1L-MoS2 and the Ag NW network, it was determined that a strong SP and strain relaxation effect influenced a greatly enhanced optical QY. The photoluminescence (PL) emission was drastically increased by a factor of 560, and the main peak was shifted to the neutral exciton of 1L-MoS2. Consequently, the overall photocurrent of the hybrid 1L-MoS2 photodetector was observed to be 250 times better than that of the pristine 1L-MoS2 photodetector. In addition, the photoresponsivity and photodetectivity of the hybrid photodetector were effectively improved by a factor of ∼1000. This study provides a new approach for realizing highly efficient optoelectronic devices based on TMDCs.

Hepatitis C Virus Induces the Localization of Lipid Rafts to Autophagosomes for Its RNA Replication.

Autophagy plays important roles in maintaining cellular homeostasis. It uses double- or multiple-membrane vesicles termed autophagosomes to remove protein aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C virus (HCV) has been shown to induce autophagy to enhance its own replication. Here we describe a procedure that combines membrane flotation and affinity chromatography for the purification of autophagosomes from cells that harbor an HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple-membrane structures with a diameter ranging from 200 nm to 600 nm. The analysis of proteins associated with HCV-induced autophagosomes by proteomics led to the identification of HCV nonstructural proteins as well as proteins involved in membrane trafficking. Notably, caveolin-1, caveolin-2, and annexin A2, which are proteins associated with lipid rafts, were also identified. The association of lipid rafts with HCV-induced autophagosomes was confirmed by Western blotting, immunofluorescence microscopy, and immunoelectron microscopy. Their association with autophagosomes was also confirmed in HCV-infected cells. The association of lipid rafts with autophagosomes was specific to HCV, as it was not detected in autophagosomes induced by nutrient starvation. Further analysis indicated that the autophagosomes purified from HCV replicon cells could mediate HCV RNA replication in a lipid raft-dependent manner, as the depletion of cholesterol, a major component of lipid rafts, from autophagosomes abolished HCV RNA replication. Our studies thus demonstrated that HCV could specifically induce the association of lipid rafts with autophagosomes for its RNA replication.IMPORTANCE HCV can cause severe liver diseases, including cirrhosis and hepatocellular carcinoma, and is one of the most important human pathogens. Infection with HCV can lead to the reorganization of membrane structures in its host cells, including the induction of autophagosomes. In this study, we developed a procedure to purify HCV-induced autophagosomes and demonstrated that HCV could induce the localization of lipid rafts to autophagosomes to mediate its RNA replication. This finding provided important information for further understanding the life cycle of HCV and its interaction with the host cells.

Effect of total number of harvested lymph nodes on survival outcomes after curative resection for gastric adenocarcinoma: findings from an eastern high-volume gastric cancer center.

BACKGROUND: Greater lymph node retrieval in gastric cancer improves staging accuracy and may improve survival from increased clearance of nodal micrometastasis. This retrospective cohort study investigated if more lymph nodes removed in gastric cancer increases survival and if such effect is stage-specific due to differential risks of nodal micrometastasis and systemic disease. METHODS: The prospectively collected database of curatively resected gastric cancer patients in National Cancer Center, South Korea between 2000 and 2009 was reviewed. Disease-free survival (DFS) and overall survival (OS) for all patients and for each stage according to number of lymph nodes examined (1-30, 31-45, > 45) were analyzed. RESULTS: Of 4049 patients, 96.6% and 98.4% underwent D2 (perigastric and extragastric) lymphadenectomy and had ≥ 15 lymph nodes examined. Mean number of nodes examined was 43. Five-year OS & DFS rates were 83.3% and 80.7%. Patients with > 45 nodes examined had significantly lower DFS (p = 0.002) and OS (p = 0.007) compared to those with 1-30 and 31-45 nodes. However, proportion of patients with > 45 nodes examined increased with stage (p = 0.0005). Per stage, there was no significant difference in DFS and OS according to number of nodes examined except for stage IIIA favoring more nodes (p = 0.018 and p = 0.044, respectively). Similar trend was seen in stage IIB. Number of examined nodes positively correlated with number of pathologic nodes for all patients (r = 0.144, p < .001) but not for stage IIB and IIIA. Number of nodes examined was a significant survival predictor in stage IIIA. CONCLUSION: Greater lymph node harvest showed improved survival in intermediate-stage gastric cancer.

Role of the Growth Temperature in MoS2 Growth by Chemical Vapor Deposition.

In this paper, we discuss the effect of synthesis temperature on the lateral growth of MoS2 thin films in chemical vapor deposition. With increasing temperature, surface coverage with MoS2 triangular islands is significantly improved due to an increase in the density of nuclei and fully continuous MoS2 thin film is grown when the growth temperature reached 800 °C. The MoS2 triangular islands grown at the temperature from 650 to 750 °C are monolayer and highly crystalline, whereas the large-area continuous film grown at the temperature of 800 °C is composed of double-layer or overlapping MoS2 nanosheets. Our research provides that synthesis temperature is the key to growth large area and high quality single crystal MoS2 films.

TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism.

Invasion by infectious pathogens can elicit a range of cytokine responses from host cells. These cytokines provide the initial host defense mechanism. In this report, we demonstrate that TNF-α, a pro-inflammatory cytokine, can be induced by hepatitis C virus (HCV) in its host cells in a biphasic manner. The initial induction of TNF-α by HCV was prompt and could be blocked by the antibody directed against the HCV E2 envelope protein and by chemicals that inhibit endocytosis, indicating the specificity of endocytic uptake of HCV in this induction. Further studies indicated that the induction of TNF-α was dependent on toll-like receptors 7 and 8 (TLR7/8) but not on other intracellular pattern recognition receptors. Consistently, siRNA-mediated gene silencing of the downstream effectors in the TLR7/8 signaling pathway including MyD88, IRAK1, TRAF6, TAK1 and p65 NF-κB suppressed the expression of TNF-α. The role of p65 NF-κB in the induction of TNF-α via transcriptional up-regulation was further confirmed by the chromatin immunoprecipitation assay. TNF-α induced by HCV could activate its own receptor TNFR1 on hepatocytes to suppress HCV replication. This suppressive effect of TNF-α on HCV was due to its role in supporting interferon signaling, as the suppression of its expression led to the loss of IFNAR2 and impaired interferon signaling and the induction of interferon-stimulated genes. In conclusion, our results indicate that hepatocytes can sense HCV infection via TLR7/8 to induce the expression of TNF-α, which inhibits HCV replication via an autocrine mechanism to support interferon signaling.

Expression of aldo-keto reductase family 1, member C14 during ovulation in the rat.

The potent androgen 5α-dihydrotestosterone is metabolized to the weak androgen 5α-androstane-3α, 17ß-diol (3α-diol) by the enzyme aldo-keto reductase family 1, member C14 (Akr1c14) in rodents. The purpose of the present study was to investigate the regulation of Akr1c14 expression during the ovulatory process in rat ovaries. Northern blot analysis revealed that treatment of immature rats with equine chorionic gonadotropin resulted in lowered Akr1c14 expression, whereas subsequent treatment with human chorionic gonadotropin (hCG) increased ovarian Akr1c14 expression within 3 h. In situ hybridization analysis showed that Akr1c14 mRNA was localized in granulosa cells of growing follicles before hCG treatment, but it was also expressed in granulosa cells of preovulatory follicles after hCG treatment. Akr1c14 protein expression increased after 6 h of hCG treatment and was sustained at high levels until 12 h. The levels of 3α-diol in preovulatory follicles isolated from ovaries in vivo were fluctuated by hCG treatment; decreased at 6 h and increased at 9 h. Human CG-induced Akr1c14 expression was suppressed by treatment with the progesterone receptor antagonist RU486, but not with the cyclooxygenase inhibitor indomethacin. Taken together, these findings demonstrate the induction of Akr1c14 by hCG in granulosa cells of rat preovulatory follicles that was regulated by progesterone receptor antagonist.

Altered Gene and Protein Expressions in Torn Rotator Cuff Tendon Tissues in Diabetic Patients.

PURPOSE: To analyze and compare the gene and protein expression characteristics in torn rotator cuff tendon tissues between diabetic and nondiabetic patients. METHODS: This was a pilot study. Twelve samples of rotator cuff tendon tissue from diabetic patients (mean age, 62.3 ± 9.9 years) and 12 age- and sex-matched nondiabetic tendon tissues (62.3 ± 9.9 years) were acquired from the torn tendon end of medium rotator cuff tears during arthroscopic surgery, after applying the same inclusion and exclusion criteria. Expressions of various genes of interest, including collagens I and III, matrix metalloprotease (MMP)-2, MMP-3, MMP-9, MMP-13, interleukin (IL)-1, IL-6, insulin-like growth factor-1, vascular endothelial growth factor, tenomodulin, tumor necrosis factor-α, and p53, were analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, immunohistochemistry and western blot assay were performed for the genes that revealed significantly different expressions in real-time qRT-PCR between groups. RESULTS: Gene expression levels of MMP-9, MMP-13, IL-6, and tenomodulin were significantly higher in the diabetic than in the nondiabetic group by real-time qRT-PCR analyses (P = .011, .004, .009, and .010, respectively). The density of cells expressing MMP-9 and IL-6 was significantly increased in the torn tendons of the diabetic patients on immunohistochemical analysis, and the density of MMP-9 and IL-6 protein expressions was significantly higher in the diabetic group on western blot (P = .018 and .044, respectively). CONCLUSIONS: Diabetic torn cuff tendon tissues showed MMP-9 and IL-6 overexpressions compared with controls. CLINICAL RELEVANCE: The overexpressions of MMP-9 and IL-6 may be one of the explanations for the high healing failure rate after rotator cuff repair in the diabetic patients.

Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA Specimens.

Molecular markers are helpful diagnostic tools, particularly for cytologically indeterminate thyroid nodules. Preoperative RET/PTC1 rearrangement analysis in BRAF and RAS wild-type indeterminate thyroid nodules would permit the formulation of an unambiguous surgical plan. Cycle threshold values according to the cell count for detection of the RET/PTC1 rearrangement by real-time reverse transcription-polymerase chain reaction (RT-PCR) using fresh and routine air-dried TPC1 cells were evaluated. The correlation of RET/PTC1 rearrangement between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded (FFPE) specimens was analyzed. RET/PTC1 rearrangements of 76 resected BRAF and RAS wild-type classical PTCs were also analyzed. Results of RT-PCR and the Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used, expression of RET/PTC1 rearrangement was detectable after 35 and 33 PCR cycles, respectively. The results of RET/PTC1 rearrangement in 10 FNA and paired FFPE papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty-nine (38.2%) of 76 BRAF and RAS wild-type classical PTCs had RET/PTC1 rearrangement. Comparison of RET/PTC1 rearrangement analysis between RT-PCR and the Nanostring showed moderate agreement with a κ value of 0.56 (p = 0.002). The RET/PTC1 rearrangement analysis by RT-PCR using routine air-dried FNA specimen was confirmed to be technically applicable. A significant proportion (38.2%) of the BRAF and RAS wild-type PTCs harbored RET/PTC1 rearrangements.

Regioisomer-dependent endo- and exocyclic coordination of bis-dithiamacrocycles.

Syntheses of the regioisomers of bis-dithiamacrocycle and the regioisomer-controlled endo- and exocyclic coordination behaviors are reported. Direct bis-cyclization reaction of 1,2,4,5-tetra(bromomethyl)benzene with 3,6-dioxa-1,8-octanedithiol led to a mixture of two bis-dithiamacrocycle regioisomers (ortho-type; o-bis-L and meta-type; m-bis-L) which were separated by recrystallization and column chromatography. When the two isomers were reacted with AgPF6, o-bis-L gave an endocyclic one-dimensional (1-D) coordination polymer {[Ag3(o-bis-L)2(CH3CN)](PF6)3·2CH3CN}n (1) with a 3:2 (metal-to-ligand) stoichiometry, while m-bis-L afforded an exocoordination-based 1-D polymeric complex {[Ag(m-bis-L)](PF6)}n (2) with a 2:2 stoichiometry. The observed endo- and exocoordination modes depending on the isomers were discussed in terms of the S···S distances in the bis-dithiamacrocycle isomers. Due to the closer S···S distance in each macrocyclic ring, o-bis-L is suitable for the endocoordination. However, m-bis-L forms an exocyclic complex because the S···S distance between two macrocyclic rings is shorter than that in one macrocyclic ring. NMR experiments also revealed that o-bis-L and m-bis-L form the endo- and the exocyclic complexes, respectively, in solution.

Distortional supramolecular isomers of polyrotaxane coordination polymers: photoreactivity and sensing of nitro compounds.

Distortional isomers, or bond-stretch isomers, differ only in the length of one or more bonds, which is due to crystallographic disorder in most cases. The term distortional isomerism is introduced to describe the structures of polyrotaxane 2D coordination polymers (CPs) that differ only by the relative positions in the neighboring entangled axles. A large ring and a long spacer ligand in 2D CPs yielded four different supramolecular isomers, of which two have an entangled polyrotaxane structure. One pair of C=C bonds in the spacer ligand is well-aligned in one isomer and undergoes [2+2] cycloaddition reaction, whereas the other isomer is photoinert. They also have different sensing efficiency for several aromatic nitro compounds. However, both isomers show selective PL quenching for the Brady's reagent. Structurally similar supramolecular isomers with different photochemical reactivity and sensing abilities appear to be unprecedented.

Skin-Attached Arrayed Piezoelectric Sensors for Continuous and Safe Monitoring of Oculomotor Movements.

Abnormal oculomotor movements are known to be linked to various types of brain disorders, physical/mental shocks to the brain, and other neurological disorders, hence its monitoring can be developed into a simple but effective diagnostic tool. To overcome the limitations in the current eye-tracking system and electrooculography, a piezoelectric arrayed sensor system is developed using single-crystalline III-N thin-film transducers, which offers advantages of mechanical flexibility, biocompatibility, and high electromechanical conversion, for continuous monitoring of oculomotor movements by skin-attachable, safe, and highly sensitive sensors. The flexible piezoelectric eye movement sensor array (F-PEMSA), consisting of three transducers, is attached to the face temple area where it can be comfortably wearable and can detect the muscles' activity associated with the eye motions. Output voltages from upper, mid, and lower sensors (transducers) on different temple areas generate discernable patterns of output voltage signals with different combinations of positive/negative signs and their relative magnitudes for the various movements of eyeballs including 8 directional (lateral, vertical, and diagonal) and two rotational movements, which enable various types of saccade and pursuit tests. The F-PEMSA can be used in clinical studies on the brain-eye relationship to evaluate the functional integrity of multiple brain systems and cognitive processes.

Enhanced luminous efficacy in phosphor-converted white vertical light-emitting diodes using low index layer.

We demonstrated improved luminous efficacy for GaN-based vertical light emitting diodes (VLEDs) employing a low index layer composed of silicon dioxide (SiO(2)) on the top surface. Three-dimensional ðnite-difference time-domain simulations for the fabricated VLED chip show that the penetration ratio of the emitted/reflected light into the VLED chip decreased by approximately 20% compared to a normal VLED chip. This result is in good agreement with an empirical study stating that white VLEDs having a SiO(2) layer exhibit an 8.1% higher luminous efficacy than white VLEDs with no layer at an injection current of 350 mA. Photons penetrating into the VLED chip, which become extinct in the VLED chip, are reflected from the SiO(2) layer due to the index contrast between the SiO(2) layer and epoxy resin containing phosphor, with no degradation of the light-extraction efficiency of the VLED chip. As such, this structure can contribute to the enhancement of the luminous efficacy of VLEDs.