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PMTPV elevated the accumulation and cytotoxicity of DXR in the spheroids. Similar results were observed by knockdown of CLDN1. Furthermore, the sensitivities to cisplatin (CDDP), docetaxel, and gefitinib were enhanced by PMTPV. The level of CLDN1 expression in CDDP-resistant cells was higher than that in parental A549 cells, which was reduced by PMTPV. PMTPV restored the toxicity to DXR in the CDDP-resistant cells. Our data suggest that PMTPV may become a novel chemosensitizer for lung adenocarcinoma.Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential diagnostic, differential, progression, and prognostic markers in IBD. A Pubmed, Web of Knowledge, and Scopus search of original articles on OSMs in IBD, published between January 2000 and April 2020, was conducted. Out of 874 articles, 79 eligible studies were identified and used to prepare the interpretative synthesis. Antioxidants followed by lipid peroxidation markers were the most popular and markers of oxidative DNA damage the least popular. There was a disparity in the number of retrieved papers evaluating biomarkers in the adult and pediatric population (n = 6). Of the reviewed OSMs, a promising performance has been reported for serum total antioxidant status as a mucosal healing marker, mucosal 8-OHdG as a progression marker, and for multi-analyte panels of lipid peroxidation products assessed non-invasively in breath as diagnostic and differential markers in the pediatric population. Bilirubin, in turn, was the only validated marker. There is a desperate need for non-invasive biomarkers in IBD which, however, will not be met in the near future by oxidative stress markers as they are promising but mostly at the early research phase of discovery.Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid-liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation.The article presents the results of long-term field tests and their mathematical analysis regarding the impacts of innovative phase change materials on the energy efficiency of composite windows with various glazing parameters. Research was conducted on six glazing combinations throughout the heating season in a temperate climate in Rzeszów (Poland). The empirical results obtained during the spring months showed an improvement in the monthly heat balance for windows with phase change materials compared to the reference window by as much as 34.09%. In addition, the empirical results allowed the development and verification of a mathematical model describing the transport and distribution of heat within a window with a phase change heat accumulator. The model was made using equations of non-stationary heat flow and an explicit finite difference method using calorimetric thermograms describing the phase change eutectic mixture used in the research. Carrying out the Snedecor-Fischer test proved the statistical adequacy of the developed model in 4 out of 6 tested combinations of glazing units. Good matching of the empirical and theoretical quantities was also confirmed using the quasi-Newton method. The article is a solution to the problem of the effective use of solar energy within transparent building partitions, while presenting a useful mathematical tool that determines potential thermal gains in various climatic conditions.Chronic hepatitis B virus (HBV) infection remains a global health threat and affects hundreds of millions worldwide. Small molecule compounds that mimic natural antagonists of inhibitor of apoptosis (IAP) proteins, known as Smac-mimetics (second mitochondria-derived activator of caspases-mimetics), can promote the death of HBV-replicating liver cells and promote clearance of infection in preclinical models of HBV infection. The Smac-mimetic birinapant is a substrate of the multidrug resistance protein 1 (MDR1) efflux pump, and therefore inhibitors of MDR1 increase intracellular concentration of birinapant in MDR1 expressing cells. Liver cells are known to express MDR1 and other drug pump proteins. In this study, we investigated whether combining the clinical drugs, birinapant and the MDR1 inhibitor zosuquidar, increases the efficacy of birinapant in killing HBV expressing liver cells. We showed that this combination treatment is well tolerated and, compared to birinapant single agent, was more efficient at inducing death of HBV-positive liver cells and improving HBV-DNA and HBV surface antigen (HBsAg) control kinetics in an immunocompetent mouse model of HBV infection. Thus, this study identifies a novel and safe combinatorial treatment strategy to potentiate substantial reduction of HBV replication using an IAP antagonist.In this work, the localization of reactive compatibilizer (RC, containing poly(methyl methacrylate) (PMMA) backbone with randomly distributed glycidyl methacrylate (GMA) on it) at the polyvinylidene fluoride/poly(l-lactic acid) (PVDF/PLLA) interface has been manipulated by means of GMA contents. At the very beginning of mixing, RC tends to stay in the PVDF phase due to the miscibility between PVDF and PMMA. Upon further shearing, more and more PLLA chains have been grafted on PMMA backbone, producing PLLA-g-PMMA copolymer. The balanced stress on two sides accounts for the localization of compatibilizers at the PVDF/PLLA interface. Finally, the stress of the PLLA side has been enhanced remarkably due to the higher graft density of PLLA, resulting in the enrichment of the copolymer in the PLLA matrix. The migration of RC from the PVDF phase to the immiscible interface and PLLA matrix can be accelerated by employing RC with higher GMA content. Furthermore, the compatibilizer localization produces a significant influence on the morphology and ductility of the PVDF/PLLA blend. Only when the compatibilizers precisely localize at the interface, the blend exhibits the smallest domain and highest elongation at break. Our results are of great significance for not only the fabrication of PLLA with high ductility, but also the precise localization of compatibilizers at the interface of the immiscible blend.Caprine arthritis-encephalitis virus (CAEV), a lentivirus, relies on the action of the Rev protein for its replication. The CAEV Rev fulfills its function by allowing the nuclear exportation of partially spliced or unspliced viral mRNAs. In this study, we characterized the nuclear and nucleolar localization signals (NLS and NoLS, respectively) and the nuclear export signal (NES) of the CAEV Rev protein. These signals are key actors in the nucleocytoplasmic shuttling of a lentiviral Rev protein. Several deletion and alanine substitution mutants were generated from a plasmid encoding the CAEV Rev wild-type protein that was fused to the enhanced green fluorescent protein (EGFP). Following cell transfection, images were captured by confocal microscopy and the fluorescence was quantified in the different cell compartments. The results showed that the NLS region is localized between amino acids (aa) 59 to 75, has a monopartite-like structure and is exclusively composed of arginine residues. The NoLS was found to be partially associated with the NLS. Finally, the CAEV Rev protein's NES mapped between aa 89 to 101, with an aa spacing between the hydrophobic residues that was found to be unconventional as compared to that of other retroviral Rev/Rev-like proteins.Despite efforts to reduce its incidence, tuberculosis continues to burden the rapidly aging Korean society. This study aimed to investigate the current trend of tuberculosis burden in Korea and its projections to 2040. We used National Health Insurance claims data to calculate the disability-adjusted life years due to tuberculosis in Korea. Disability-adjusted life years were measured by summing the years of life lost and the years lived with disability using an incidence-based approach. We modeled the incidence rates using a time-series model for the projection of disability-adjusted life years accrued from 2020 to 2040. The total disability-adjusted life years due to tuberculosis were 69, 64, 59, and 49 disability-adjusted life years/100,000 population in 2014, 2015, 2016, and 2017, respectively. In both sexes, disability-adjusted life years were the highest in those aged ≥80 years. Projected disability-adjusted life years showed a descending trend from 38 disability-adjusted life years/100,000 in 2020, to 14 disability-adjusted life years/100,000 in 2040. Conversely, the projected disability-adjusted life years increased among females aged ≥80 years. Although the tuberculosis burden in Korea is decreasing, a high burden remains among the elderly. Therefore, interventions targeting those vulnerable are required.MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied the influence of radical prostatectomy (RP) on the expression of 12 cell-free miRNAs previously shown as potential markers of PCa (i.e., miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375 and miR-660). The relative expression of the miRNAs combined into 31 paired ratios was evaluated in the urine extracellular vesicles (EVs), clarified urine (CU) and blood plasma of healthy donors, pre- and post-RP samples of PCa patients. Nineteen miRNA ratios based on combinations of ten of the miRNAs (miR-19b, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, miR-378, miR-425, and miR-660) were altered by RP. The comparative expression analysis of the cell-free miRNA ratios between healthy donors and PCa patients revealed miR-125b/miR-30e and miR-375/miR-30e as potential markers for evaluating therapeutic efficacy. MiR-378/miR-19b, miR-425/miR-19b, miR-200/miR-30e, miR-660/miR-30e, and miR-205/miR-30e had minor prognostic value but could be used to increase the steadiness of the diagnostic system. The urine EVs had the highest potential as a source of markers.
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