Recently, various attempts have been made to solve plastic waste problems, such as development of biodegradation without producing pollution. Polystyrene (PS) is the fifth most used plastic in many industries; therefore, degrading PS becomes a critical global issue. Here, we reported Pseudomonas aeruginosa strain DSM 50071, initially isolated from the gut of the superworms, Zophobas atratus, and the PS degradation by Pseudomonas sp. DSM 50071. We examined PS degradation using electronic microscopy and measured changes in atomic composition and contact angles with water droplets on the PS surface that represents a chemical change from hydrophobicity to hydrophilicity. We have further examined chemical structural changes using X-ray photoelectron spectroscopy, Fourier-transform-infrared spectroscopy, and nuclear magnetic resonance (NMR) to confirm the formation of carbonyl groups (CO) in the oxidation pathway during PS biodegradation. In reverse transcription quantitative polymerase chain reaction analysis, the gene expression level of serine hydrolase (SH) in Pseudomonas sp. DSM 50071 was highly increased during PS degradation, and the enzyme-mediated biodegradation of PS was further confirmed by the SH inhibitor treatment test. Thus, the significance of these findings goes beyond the discovery of a novel function of Pseudomonas sp. DSM 50071 in the gut of superworms, highlighting a potential solution for PS biodegradation.
Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a member of an evolutionarily conserved family of protein kinases that belongs to the CMGC group of kinases. DYRK1A, encoded by a gene located in the human chromosome 21q22.2 region, has attracted attention due to its association with both neuropathological phenotypes and cancer susceptibility in patients with Down syndrome (DS). Inhibition of DYRK1A attenuates cognitive dysfunctions in animal models for both DS and Alzheimer's disease (AD). Furthermore, DYRK1A has been studied as a potential cancer therapeutic target because of its role in the regulation of cell cycle progression by affecting both tumor suppressors and oncogenes. Consequently, selective synthetic inhibitors have been developed to determine the role of DYRK1A in various human diseases. Our perspective includes a comprehensive review of potent and selective DYRK1A inhibitors and their forthcoming therapeutic applications.
The 6′-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell Sadenosyl-L-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6′position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and N 6 -methyladenosine analogues 2a−e showed potent inhibition against SAH hydrolase, while only the adenosine derivatives 2a−c exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6′,6′-Difluoroaristeromycin (2c) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug 3a also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6′-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.
The use of DN in adult valve surgery including complex procedures may confer acceptable outcomes comparable to or even superior to those obtained with the use of blood cardioplegia.
Colorectal cancer (CRC) is a major global health concern. Its early diagnosis is extremely important, as it determines treatment options and strongly influences the length of survival. Histologic diagnosis can be made by pathologists based on images of tissues obtained from a colonoscopic biopsy. Convolutional neural networks (CNNs)-i.e., deep neural networks (DNNs) specifically adapted to image data-have been employed to effectively classify or locate tumors in many types of cancer. Colorectal histology images of 28 normal and 29 tumor samples were obtained from the National Cancer Center, South Korea, and cropped into 6806 normal and 3474 tumor images. We developed five modifications of the system from the Visual Geometry Group (VGG), the winning entry in the classification task in the 2014 ImageNet Large Scale Visual Recognition Competition (ILSVRC) and examined them in two experiments. In the first experiment, we determined the best modified VGG configuration for our partial dataset, resulting in accuracies of 82.50%, 87.50%, 87.50%, 91.40%, and 94.30%, respectively. In the second experiment, the best modified VGG configuration was applied to evaluate the performance of the CNN model. Subsequently, using the entire dataset on the modified VGG-E configuration, the highest results for accuracy, loss, sensitivity, and specificity, respectively, were 93.48%, 0.4385, 95.10%, and 92.76%, which equates to correctly classifying 294 normal images out of 309 and 667 tumor images out of 719.
We report a very rare case of hemangioblastomatosis that developed after surgical removal of a solitary cerebellar hemangioblastoma (HB). A 51-yr-old man presented with back pain 10 yr after undergoing surgery for cerebellar HB. Magnetic resonance imaging showed numerous mass lesions along the entire neuraxis accompanied by prominent leptomeningeal enhancement. Genomic DNA analysis showed no mutation in the von Hippel-Lindau (VHL) genes. A surgical specimen obtained from a lesion in the cauda equina showed pathological findings identical to those of the cerebellar HB that had been resected 10 yr earlier. External beam radiation therapy and radiosurgery were subsequently performed; however, the patient succumbed one year after receiving the diagnosis of hemangioblastomatosis. The reduction of tumor cell spillage during surgery and regular long-term follow-up are recommended for patients with HBs.
Paper-based microfluidic analytical devices (μPADs) have recently attracted attention as a point-of-care test kit because of their low cost and nonrequirement for external forces. To directly detect biomarkers in whole blood, however, they need to be assembled with a filter such as a plasma separation membrane (PSM) because the color of the blood cells interferes with the colorimetric assay. However, this assembly process is rather complicated and cumbersome, and the fluid does not uniformly move to the detection zone when the adhesion between the paper and PSM is not perfect. In this study, we report a simple three-dimensional (3D) printing method for fabricating PSM-integrated 3D-μPADs made of plastics without the need for additional assembly. In detail, PSM was coated with parylene C to prevent its dissolution from organic solvent during 3D printing. Then, the coated PSM was superimposed on the paper. Detection zones and a reservoir were printed on the paper and PSM via liquid photopolymerization, using a digital light processing printer. The limit of detection of the PSM-integrated 3D-μPADs for glucose in whole blood was 0.3 mM, and these devices demonstrated clinically relevant performance on diabetes patient blood samples. Our 3D-μPADs can also simultaneously detect multiple metabolic disease markers including glucose, cholesterol, and triglycerides in whole blood. Our results suggest that our printing method is useful for fabricating 3D-μPADs integrated with PSM for the direct detection of biomarkers in whole blood.
Chemiluminescence immunoassays have been widely employed for diagnosing various diseases. However, because of the extremely low intensity chemiluminescence signals, highly sensitive transducers, such as photomultiplier tubes and image sensors with cooling devices, are required to overcome this drawback. In this study, a hypersensitive photosensor was developed based on cesium lead bromide (CsPbBr 3 ) perovskite quantum dots (QDs) with sufficient high sensitivity for chemiluminescence immunoassays. First, CsPbBr 3 QDs with a highly uniform size, that is, 5 nm, were synthesized under thermodynamic control to achieve a high size confinement effect. For the fabrication of the photosensor, MoS 2 nanoflakes were used as an electron transfer layer and heat-treated at an optimum temperature. Additionally, a parylene-C film was used as a passivation layer to improve the physical stability and sensitivity of the photosensor. In particular, the trap states on the CsPbBr 3 QDs were reduced by the passivation layer, and the sensitivity was increased. Finally, a photosensor based on CsPbBr 3 QDs was employed in chemiluminescence immunoassays for the detection of human hepatitis B surface antigen, human immunodeficiency virus antibody, and alpha-fetoprotein (AFP, a cancer biomarker). When compared with the conventionally used equipment, the photosensor was determined to be feasible for application in chemiluminescence immunoassays.
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