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Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery ligation. We studied the molecular mechanisms underlying adiponectin's cardio‐protective effects in adiponectin knockout (Ad‐KO) compared with wild‐type (WT) mice subjected to ischemia by coronary artery ligation and H9c2 cardiomyocyte cell line exposed to hypoxia. Systemic infusion of a cathepsin‐B activatable near‐infrared probe as a biomarker for autophagy and detection via noninvasive three‐dimensional fluorescence molecular tomography combined with computerized tomography to quantitate temporal changes, indicated increased activity in the myocardium of WT mice after myocardial infarction which was attenuated in Ad‐KO. Seven days of ischemia increased myocardial adiponectin accumulation and elevated ULK1/AMPK phosphorylation and autophagy assessed by Western blotting for LC3 and p62, an outcome not observed in Ad‐KO mice. Cell death, assessed by TUNEL analysis and the ratio of Bcl‐2:Bax, plus cardiac dysfunction, measured using echocardiography with strain analysis, were exacerbated in Ad‐KO mice. Using cellular models, we observed that adiponectin stimulated autophagy flux in isolated primary adult cardiomyocytes and increased basal and hypoxia‐induced autophagy in H9c2 cells. Real‐time temporal analysis of caspase‐3/7 activation and caspase‐3 Western blot indicated that adiponectin suppressed activation by hypoxia. Hypoxia‐induced mitochondrial reactive oxygen species production and cell death were also attenuated by adiponectin. Importantly, the ability of adiponectin to reduce caspase‐3/7 activation and cell death was not observed in autophagy‐deficient cells generated by CRISPR‐mediated deletion of Atg7. Collectively, our data indicate that adiponectin acts in an autophagy‐dependent manner to attenuate cardiomyocyte caspase‐3/7 activation and cell death in response to hypoxia in vitro and ischemia in mice. [ABSTRACT FROM AUTHOR]

Abstract: A multilayer ceramic capacitor (MLCC) contains layers of ceramics as the dielectric materials. It has been known that Class 2 MLCCs, made of ferroelectric ceramics such as barium titanate, tend to suffer from electromechanical coupling hence vibration, which leads to the generation of acoustic humming noise, a source of annoyance in many modern electronic devices. In this article, a repoling method to control the electromechanical properties and the resulting vibration of MLCCs is presented. The repoling protocol hinges on the understanding that two independent mechanisms are responsible for the electromechanical coupling in MLCCs: piezoelectricity and electrostriction of the ceramic layers. The vibration due to piezoelectricity is linearly proportional to the input voltage, whereas the vibration due to electrostriction shows a quadratic dependence. Given the DC bias and the AC input voltage under normal operating conditions, the vibration is composed of the fundamental component at the frequency of the AC input and the second harmonic component spawned by the quadratic nonlinearity of electrostriction. It is demonstrated that by engineering the coefficients of piezoelectricity and electrostriction of the ceramic layers through a carefully designed repoling treatment, vibration reduction can be achieved for both the fundamental and second harmonic components. Especially, the fundamental component of vibration can be reduced significantly, as the piezoelectric effect is made to offset the electrostrictive effect. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare human epidermal growth factor 2 ( HER2) status in primary colorectal cancer and paired liver or lung metastasis. Gene amplification of HER2 has been intensively evaluated in contemporary oncology, especially in breast and stomach cancer. The knowledge of HER2 status in primary and metastatic sites may be of potential value for therapeutic decision making in metastatic colon cancer. The HER2 status was assessed by fluorescence in situ hybridization ( FISH) and immunohistochemistry ( IHC) in 94 colorectal cancer with corresponding liver or lung metastases. HER2 amplification was present in 19 of the 188 (10.1%) of both primary and metastases combined. Four (4.6%) patients showed HER2 amplification in the metastasis and 10 (10.6%) patients showed HER2 amplification in the primary tumor. In 14 cases (14.8%), the HER2 status of the primary lesions was different from that of the associated metastases. The presence of HER2 overexpression in KRAS mutant colon cancer was found in 5.3%. No relationship was found between HER2 expression and KRAS status ( P = 0.486). The evidence of HER2 positive metastatic lesion and primary colorectal cancer suggest that HER2 assessment might be considered in selected cases when this may help change the therapeutic decision. [ABSTRACT FROM AUTHOR]

Today's mobile and remote construction applications, such as tracking of materials, equipment, and workers, demand high reliability and scalability of wireless sensor networks for a large-scale construction site. In particular, identifying the location of distributed mobile entities throughout wireless communications becomes the primary task to realize the remote tracking and monitoring of the construction assets. Even though several alternative solutions have been introduced by utilizing recent technologies, such as radio frequency identification (RFID) and the global positioning system (GPS), they could not provide a solid direction to accurate and scalable tracking frameworks in large-scale construction domains due to limited capability and inflexible networking architectures. This article introduces a new tracking architecture using wireless sensor modules and shows an accuracy performance using a numerical simulation approach based on the time-of-flight method. By combining radio frequency (RF) and ultrasound (US) signals, the simulation results showed an enhanced accuracy performance over the utilization of an RF signal only. The proposed approach can provide potential guidelines for further exploration of hardware/software design and for experimental analysis to implement the framework of tracking construction assets. [ABSTRACT FROM AUTHOR]

An unprecedented silver‐mediated intramolecular oxy‐argentation of 3‐amidoaryne precursors that quickly generates a heteroarylsilver species is developed. AgF acts as both a stoichiometric fluoride source and a reagent for the formation of a benzoxazolylsilver intermediate via aryne generation. Pd‐catalyzed coupling reactions of (hetero)aryl iodides with a silver species, generated in situ, allow for the synthesis of various C7‐arylated benzoxazoles. As a result, an aryl group is selectively introduced into the meta‐position of 3‐amidobenzyne precursors. Mechanistic studies have indicated the presence of a benzoxazolylsilver intermediate and revealed that the reaction proceeds via an intramolecular oxy‐argentation process, which is initiated by a direct fluoride attack on the silyl group. [ABSTRACT FROM AUTHOR]

Background: After pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist. Objectives: We aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes. Methods: Data were retrospectively collected from the hospital‐based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited. Results: A total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P =.030), lower influenza vaccination (27.9% vs 43.9%, P <.001) and pneumococcal vaccination rates (41.0% vs 51.9%, P <.001), and fewer underlying diseases (67.5% vs 74.0%, P =.035) than the A(H3N2) group. Influenza A subtypes were not associated with pneumonia risk (adjusted odds ratios [AOR] of A(H1N1)pdm09: 0.7 [95% confidence interval [CI]: 0.4‐1.2, P =.172]) and in‐hospital mortality (hazard ratio (HR) of A(H1N1)pdm09: 1.0 (95% CI: 0.3‐3.1, P =.983)). Influenza vaccination reduced in‐hospital mortality in hospitalized patients (HR: 0.3 (95% CI: 0.1‐0.7), P =.005). Conclusions: A(H1N1)pdm09 infection was more common in younger patients without significant difference in pneumonia risk and in‐hospital mortality between subtypes. Influenza vaccination was associated with reduced in‐hospital mortality. [ABSTRACT FROM AUTHOR]

The advancement of non‐fullerene acceptors with crescent‐shaped geometry has led to the need for polymer donor improvements. Additionally, there is potential to enhance the photovoltaic parameters in high‐efficiency organic solar cells (OSCs). The random copolymerization method is a straightforward and effective strategy to further optimize photoactive morphology and enhance device performance. However, finding a suitable third component in terpolymers remains a crucial challenge. In this study, a series of terpolymer donors (PTF3, PTF5, PTF10, PTF20, and PTF50) is synthesized by introducing varying amounts of the trifluoromethyl‐substituted unit (CF3) into the PM6 polymer backbone. Even subtle changes in the CF3 content can significantly enhance all the photovoltaic parameters due to the optimized energy levels, molecular aggregation/miscibility, and bulk‐heterojunction morphology of the photoactive materials. Thus, the best binary OSC based on the PTF5:Y6‐BO achieves an outstanding power conversion efficiency (PCE) of 18.2% in the unit cell and a PCE of 11.6% in the sub‐module device (aperture size: 54.45 cm2), when using halogen‐free solvent o‐xylene. This work showcases the remarkable potential of the easily accessible CF3 unit as a key constituent in the construction of terpolymer donors in high‐performance OSCs. [ABSTRACT FROM AUTHOR]

Glia contribute to synapse elimination through phagocytosis in the central nervous system. Despite the important roles of this process in development and neurological disorders, the identity and regulation of the "eat‐me" signal that initiates glia‐mediated phagocytosis of synapses has remained incompletely understood. Here, we generated conditional knockout mice with neuronal‐specific deletion of the flippase chaperone Cdc50a, to induce stable exposure of phosphatidylserine, a well‐known "eat‐me" signal for apoptotic cells, on the neuronal outer membrane. Surprisingly, acute Cdc50a deletion in mature neurons causes preferential phosphatidylserine exposure in neuronal somas and specific loss of inhibitory post‐synapses without effects on other synapses, resulting in abnormal excitability and seizures. Ablation of microglia or the deletion of microglial phagocytic receptor Mertk prevents the loss of inhibitory post‐synapses and the seizure phenotype, indicating that microglial phagocytosis is responsible for inhibitory post‐synapse elimination. Moreover, we found that phosphatidylserine is used for microglia‐mediated pruning of inhibitory post‐synapses in normal brains, suggesting that phosphatidylserine serves as a general "eat‐me" signal for inhibitory post‐synapse elimination. SYNOPSIS: Neuronal‐specific deletion of the flippase chaperone Cdc50a leads to exposure of phosphatidylserin on neuronal outer membranes causing specific loss of inhibitory post‐synapses and seizures. Microglial phagocytosis via the phagocytic receptor MERTK promotes inhibitory post‐synapse elimination in Cdc50a cKO brains. Inhibitory post‐synapses in normal juvenile brains also use phosphatidylserine for synapse elimination, suggesting that phosphatidylserine exposure functions as an "eat‐me" signal for microglia‐dependent inhibitory post‐synapse elimination. Neuronal Cdc50a deletion induces rapid lethality with appearance of audiogenic seizure.Neuronal Cdc50a deletion causes the specific loss of inhibitory post‐synapses without affecting other synapses.Ablating microglia or deleting microglial Mertk rescues the loss of inhibitory post‐synapses and seizure behaviors in Cdc50a cKO mice.Microglial Mertk deletion increases the number of phosphatidylserine‐exposed inhibitory post‐synapses in the wild‐type juvenile brains. [ABSTRACT FROM AUTHOR]

Glycyl‐tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20–58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13–1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1‐containing EVs (GARS1‐EVs). Among the identified factors, insulin‐like growth factor II receptor, and vimentin also contributed to the anti‐cancer activity of GARS1‐EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis. [ABSTRACT FROM AUTHOR]

Glycyl‐tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20–58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13–1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1‐containing EVs (GARS1‐EVs). Among the identified factors, insulin‐like growth factor II receptor, and vimentin also contributed to the anti‐cancer activity of GARS1‐EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis. [ABSTRACT FROM AUTHOR]

Premise: When plants are exposed to stress conditions, irreversible damage can occur, negatively impacting yields. It is therefore important to detect stress symptoms in plants, such as the accumulation of anthocyanin, as early as possible. Methods and Results: Twenty‐two regression models in five color spaces were trained to develop a prediction model for plant anthocyanin levels from digital color imaging data. Of these, a quantile random forest regression model trained with standard red, green, blue (sRGB) color space data most accurately predicted the actual anthocyanin levels. This model was then used to noninvasively monitor the spatial and temporal accumulation of anthocyanin in Arabidopsis thaliana leaves. Conclusions: The digital imaging–based nature of this protocol makes it a low‐cost and noninvasive method for the detection of plant stress. Applying a similar protocol to more economically viable crops could lead to the development of large‐scale, cost‐effective systems for monitoring plant health. [ABSTRACT FROM AUTHOR]

Background and Purpose: We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects in the hippocampus and whether its up-regulation contributes to the enhance of a neuroprotective system in the adult brain.Experimental Approach: To determine the presence of a neuroprotective system in the hippocampus of patients with Alzheimer's disease (AD), we examined the levels of glial fibrillary acidic protein, BDNF and ciliary neurotrophic factor (CNTF) and their receptors, tropomyocin receptor kinase B (TrkB) and CNTF receptor α(CNTFRα), in the hippocampus of AD patients. We also determined whether AAV1-Rheb(S16H) transduction stimulates astroglial activation and whether reactive astrocytes contribute to neuroprotection in models of hippocampal neurotoxicity in vivo and in vitro.Key Results: AD patients may have a potential neuroprotective system, demonstrated by increased levels of full-length TrkB and CNTFRα in the hippocampus. Further AAV1-Rheb(S16H) transduction induced sustained increases in the levels of full-length TrkB and CNTFRα in reactive astrocytes and hippocampal neurons. Moreover, neuronal BDNF produced by Rheb(S16H) transduction of hippocampal neurons induced reactive astrocytes, resulting in CNTF production through the activation of astrocytic TrkB and the up-regulation of neuronal BDNF and astrocytic CNTF which had synergistic effects on the survival of hippocampal neurons in vivo.Conclusions and Implications: The results demonstrated that Rheb(S16H) transduction of hippocampal neurons could strengthen the neuroprotective system and this intensified system may have a therapeutic value against neurodegeneration in the adult brain. [ABSTRACT FROM AUTHOR]

The efficiency of a heterojunction with intrinsic thin‐layer (HIT) solar cell with an insulator/ITO structure was discussed in this paper. First, the efficiency was analyzed by OPAL 2 simulations. Second, an insulator/ITO structure was experimentally applied to a HIT solar cell. The OPAL 2 simulations using an insulator/ITO/Si structure and a TCO/ITO/Si structure showed that the generation current density in the Si substrate increased when the insulator or TCO layer had a proper thickness. Experimentally, HfO2, a type of insulator, was deposited on a HIT solar cell with a thickness varying from 3 to 15 nm. The average efficiency of the HIT solar cell improved from 18.21% to 20.75% after HfO2 deposition. The highest efficiency was achieved for the 3‐nm‐thick HfO2/HIT solar cell structure, which exhibited the best improvement in the current density of approximately 1.5 mA/cm2. For the external quantum efficiency of the HfO2/HIT solar cell, the total absorption was improved by HfO2 deposition. The results suggest that the HfO2 layer improves the solar cell efficiency of the HIT solar cell by increasing light absorption. The simulations using an insulator or TCO/ITO/Si structures showed that the generation current density increased when the insulator or TCO layer had a proper thickness. Experimentally, the average efficiency of the HIT solar cell improved from 18.21% to 20.75% after HfO2 deposition, a type of insulator. The highest efficiency was achieved for the 3‐nm‐thick HfO2/HIT solar cell structure, which exhibited the best improvement in the current density of approximately 1.5 mA/cm2. [ABSTRACT FROM AUTHOR]

Background: The influenza virus is reportedly associated with 3‐5 million cases of severe illness and 250 000‐500 000 deaths annually worldwide. Objectives: We investigated the variation of influenza A virus in Korea and examined the association with death. Methods: A total of 13 620 cases were enrolled in the Hospital‐based Influenza Morbidity & Mortality surveillance system in Korea during 2011‐2016. Among these cases, a total of 4725 were diagnosed with influenza using RT‐PCR (influenza A; n = 3696, influenza B; n = 928, co‐infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs. Results: We found that the sequences of A/H3N2 in the 2011‐2012 season belong to subgroup 3C.1, whereas the sequences in the 2012‐2013 season pertain to subgroup 3C.2. The sequences in the 2013‐2014 and 2014‐2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease. Conclusions: In conclusion, influenza A virus clade changes occurred in Korea during the 2011‐2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions. [ABSTRACT FROM AUTHOR]

Metastatic colorectal cancer ( CRC) patients with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS) mutations are resistant to monoclonal antibody that targets the epidermal growth factor receptor such as cetuximab. BKM120 targets phosphatidylinositide-3-kinase ( PIK3 CA), but it is unknown whether BKM120 can reverse cetuximab resistance in KRAS mutant CRC. Human CRC cell lines with KRAS mutations ( DLD-1, HCT116, and LoVo) were used to test the effect of cetuximab, BKM120, and cetuximab plus BKM120 on cell proliferation in vitro and in vivo. BKM120 reduced cell proliferation in a concentration-dependent manner in the LoVo ( PI3 KCA wild type) as well as the HCT116 and DLD1 cells (that carry a PI3 KCA mutation). BKM120 only inhibited ERK phosphorylation in LoVo cells ( PIK3 CA wild type), but not in DLD1 or HCT116 cells at a concentration of 1 μmol/L. Treatment with cetuximab and BKM120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone ( P = 0.034). BKM120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation. [ABSTRACT FROM AUTHOR]

A new conjugated copolymer, poly{4,8-bis(triisopropylsilylethynyl)benzo[1,2-b:4,5-b']dithiophene-alt-4,7-bis(5-thiophen-2-yl)-5,6-difluoro-2-(heptadecan-9-yl)-2H-benzo[d][1,2,3]triazole} (PTIPSBDT--DFDTBTz), is synthesized by Stille coupling polycondensation. The synthesized polymer has a band gap energy of 1.9 eV, and it absorbs light in the range 300-610 nm. The hole mobility of a solution-processed organic thin-film transistor fabricated using PTIPSBDT--DFDTBTz is 3.8 x 10-3 cm2 V-1 s-1. Bulk heterojunction photovoltaic cells are fabricated, with a conventional device structure of ITO/PEDOT:PSS/polymer:PC71BM/Ca/Al (PC71BM = [6,6]-phenyl-C71-butyric acid methyl ester); the device shows a power conversion efficiency (PCE) of 2.86% with an open-circuit voltage (Voc) of 0.85 V, a short-circuit current density (Jsc) of 7.60 mA cm-2, and a fill factor (FF) of 0.44. Inverted photovoltaic cells with the structure ITO/ethoxylated polyethlyenimine/ polymer:PC71BM/MoO3/Ag are also fabricated; the device exhibits a maximum PCE of 2.92%, with a Voc of 0.89 V, a Jsc of 6.81 mA cm-2, and an FF of 0.48. [ABSTRACT FROM AUTHOR]

The article discusses the effectiveness of cilostazol in the treatment of patients with rheumatoid arthritis (RA). It describes the method of the study wherein a mice was induced with arthritis and treated with cilostazol. It states that cilostazol enhances apoptosis and inhibits the proliferation of synovial fibroblasts. It also emphasizes the ability of the drug to block cytokine production by the medication of the cyclic adenylic acid (cAMP)-dependent protein kinase activation.

Cilostazol increases intracellular cyclic adenosine monophosphate (cyclic AMP) levels by inhibiting type III phosphodiesterase. It was approved by the Food and Drug Administration for the treatment of intermittent claudication. Its principal actions include inhibition of platelet aggregation, antithrombotic action in cerebral ischemia, and vasodilation, mediated by increased cyclic AMP levels. In a multicenter, randomized, placebo-controlled, double-blind clinical trial, cilostazol has been shown to protect patients from recurrent cerebral infarction. It has been recently suggested that cilastozol could be useful in the treatment of transient focal cerebral ischemic injury. Beneficial effects of cilostazol in cerebral ischemic infarction and edema formation has been confirmed in rats by the magnetic resonance imaging (MRI). The preventive effect was ascribed to cAMP-dependent protein kinase (PKA)-coupled maxi-K channel activation with additional antioxidant and poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitory actions. Most recently, cilostazol has been shown to prevent vacuolation and rarefaction in the white matter of the rats subjected to chronic cerebral hypoperfusion in association with suppression of astrocyte and microglial activation. Taken together, recent experimental studies with cilostazol showed promising results in cerebral ischemia and chronic cerebral hypoperfusion. [ABSTRACT FROM AUTHOR]

Abstract: To understand the role of adventitial fibroblasts (AF) in diabetic vascular diseases, the importance of high glucose (HG, 25mM) on matrix metalloproteinase-2 (MMP-2) production in AF was determined. HG enhanced mRNA, protein and gelatinolytic activity of MMP-2. The enhanced MMP-2 activity was significantly attenuated not only by a PI3K inhibitor but also by an Akt inhibitor. These HG-induced MMP-2 responses were markedly reduced in Akt1-deficient (1KO) cells. The diminished HG-induced MMP-2 responses were completely restored by re-expression of Akt1. Both the reporter activity and electrophoretic mobility shift assay for activator protein-1 and nuclear factor-kappa B (NF-κB) were enhanced by HG, but NF-κB were not increased in 1KO cells. Furthermore, HG-induced MMP-2 responses were markedly suppressed by NF-κB decoy oligodeoxynucleotides. Based on these results, it is suggested that HG augments MMP-2 production via PI3K/Akt1/NF-κB pathway. [Copyright &y& Elsevier]