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Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. The properties of three-dimensional (3D) tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a 3D tumoroid-based screening system. We screened six pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with a matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-κB, and β-catenin, and the properties of cancer stem cells/cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited the tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors.A low noise interface ASIC for micro gyroscope with ball-disc rotor is realized in 0.5µm CMOS technology. The interface circuit utilizes a transimpedance pre-amplifier which reduces input noise. The proposed interface achieves 0.003 o/s/Hz1/2 noise density and 0.003 o/s sensitivity with ±100 o/s measure range. The functionality of the full circuit, including circuit analysis, noise analysis and measurement results, has been demonstrated.Beam pattern measurement is essential to verifying the performance of an array sonar. However, common problems in beam pattern measurement of arrays include constraints on achieving the far-field condition and reaching plane waves mainly due to limited measurement space as in acoustic water tank. For this purpose, the conventional method of measuring beam patterns in limited spaces, which transform near-field measurement data into far-field results, is used. However, the conventional method is time-consuming because of the dense spatial sampling. Hence, we devised a method to measure the beam pattern of a discrete line array in limited space based on the subarray method. In this method, a discrete line array with a measurement space that does not satisfy the far-field condition is divided into several subarrays, and the beam pattern of the line array can then be determined from the subarray measurements by the spatial convolution that is equivalent to the multiplication of beam pattern. The proposed method was verified through simulation and experimental measurement on a line array with 256 elements of 16 subarrays.The diagnosis of psychogenic nonepileptic seizures (PNES) by means of electroencephalography (EEG) is not a trivial task during clinical practice for neurologists. No clear PNES electrophysiological biomarker has yet been found, and the only tool available for diagnosis is video EEG monitoring with recording of a typical episode and clinical history of the subject. In this paper, a data-driven machine learning (ML) pipeline for classifying EEG segments (i.e., epochs) of PNES and healthy controls (CNT) is introduced. This software pipeline consists of a semiautomatic signal processing technique and a supervised ML classifier to aid clinical discriminative diagnosis of PNES by means of an EEG time series. In our ML pipeline, statistical features like the mean, standard deviation, kurtosis, and skewness are extracted in a power spectral density (PSD) map split up in five conventional EEG rhythms (delta, theta, alpha, beta, and the whole band, i.e., 1-32 Hz). Then, the feature vector is fed into three different s support existing clinical diagnosis.Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and a-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of mM dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand-receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure. Nilaparvata lugens is one of the major pests of rice and results in substantial yield loss every year. Our previous study found that the entomopathogenic fungus Metarhizium anisopliae showed effective potential for controlling this pest. However, the mechanisms underlying M. anisopliae infection of N. lugens are not well known. In the present study, we further examined the transcriptome of N. lugens at 4 h, 8 h, 16 h, and 24 h after M. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html anisopliae infection by Illumina deep sequencing. In total, 174.17 Gb of data was collected after sequencing, from which 23,398 unigenes were annotated by various databases, including 3694 newly annotated genes. The results showed that there were 246 vs 75, 275 vs 586, 378 vs 1055, and 638 vs 182 up- and downregulated differentially expressed genes (DEGs) at 4 h, 8 h, 16 h, and 24 h after M. anisopliae infection, respectively. The biological functions and associated metabolic processes of these genes were determined with the Clusters of Orthologous Groups (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases.
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