Introduction. Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. ...Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β) promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.
High serum lactate dehydrogenase (LDH) level, immunologic defects, enlarged mediastinal lymph nodes, and frequent hydration and diuresis in lymphoma patients may affect the development of pleural ...effusion (PE). The study was to assess the clinical utility of "Light criteria" and the "recommended algorithm for investigating PEs" in patients with lymphoma.The characteristics of 126 PEs of lymphoma patients who underwent diagnostic thoracentesis between January 1, 2003, and April 30, 2012, were reviewed. Using Light criteria, 29 (23%) PEs were incorrectly classified. The sensitivity for exudates in Light criteria was 88% and the specificity was only 44%. In 32 transudates, PE LDH correlated with blood LDH concentration (P < 0.001, r = 0.66). Nine transudates were misclassified as exudates (50%; 9/18) just due to PE LDH more than two-thirds the upper limits. Among the 56 bilateral PEs, 33 (59%) were exudates. Ten (63%) polymorphonuclear (PMN)-predominant exudative PEs were malignant. Infective PEs were often mononuclear (67%) rather than PMN predominant.When a patient has lymphoma with either unilateral or bilateral PE, thoracentesis for microbiological testing and cytology is imperative. Carefully clinical correlation in addition to the result from Light criteria and differential cell count is essential for prompt management.
Background/Aim: The elevated expression of interleukin-18 (IL-18) among lung cancer patients raised our curiosity to examine the role of IL-18 genotypes in lung cancer. Materials and Methods: IL-18 ...-656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 358 lung cancer cases and 716 controls were determined via the PCR-RFLP methodology. Results: The distributions of genotypic and allelic frequencies of IL-18 -607, but not those of -656 or -137, were differentially distributed between cases and controls. IL-18 -607 AC and CC genotypes were both lower (45.8% and 16.2%) in lung cancer patients compared to controls (51.4% and 24.7%). In addition, IL-18 -607 AC and CC genotypes were of significantly lower percentages both among non-smokers and smokers. Otherwise, no differential distribution was found regarding IL-18 -656 or -137. Conclusion: IL-18 -607 C allele can serve as a protective predictor for lung cancer risk in Taiwanese.
The culture environment plays an important role for stem cells' cultivation. Static or dynamic culture preserve differential potentials to affect human mesenchymal stem cells' (hMSCs) proliferation ...and differentiation. In this study, hMSCs were seeded on fiber disks and cultured in a bidirectional-flow bioreactor or spinner-flask bioreactor with a supplement of osteogenic medium. The hMSCs' proliferation, osteogenic differentiation, and extracellular matrix deposition of mineralization were demonstrated. The results showed that the spinner flask improved cell viability at the first two weeks while the bidirectional-flow reactor increased the cell proliferation of hMSCs through the four-week culture period. Despite the flow reactor having a higher cell number, a lower lactose/glucose ratio was noted, revealing that the bidirectional-flow bioreactor provides better oxygen accessibility to the cultured cells/disk construct. The changes of calcium ions in the medium, the depositions of Ca
in the cells/disk constructs, and alkaline phosphate/osteocalcin activities showed the static culture of hMSCs caused cells to mineralize faster than the other two bioreactors but without cell proliferation. Otherwise, cells were distributed uniformly with abundant extracellular matrix productions using the flow reactor. This reveals that the static and dynamic cultivations regulated the osteogenic process differently in hMSCs. The bidirectional-flow bioreactor can be used in the mass production and cultivation of hMSCs for applications in bone regenerative medicine.
Carbapenem-resistant ST11_KL64
emerged as a significant public health concern in Taiwan, peaking between 2013 and 2015, with the majority of isolates exhibiting OXA-48 as the sole carbapenemase. In ...this study, we employed whole-genome sequencing to investigate the molecular underpinnings of ST11_KL64 isolates collected from 2013 to 2021. Phylogenomic analysis revealed a notable genetic divergence between the ST11_KL64 strains in Taiwan and those in China, suggesting an independent evolutionary trajectory. Our findings indicated that the ST11_KL64_Taiwan lineage originated from the ST11_KL64 lineage in Brazil, with recombination events leading to the integration of ICE
and a 27-kb fragment at the tRNA
sites, shaping its unique genomic landscape. To further elucidate this unique sublineage, we examined the plasmid contents. In contrast to ST11_KL64_Brazil strains, which predominantly carried
, ST11_KL64_Taiwan strains exhibited the acquisition of an epidemic
-carrying IncL plasmid. Additionally, ST11_KL64_Taiwan strains consistently harbored a multi-drug resistance IncC plasmid, along with a collection of gene clusters that conferred resistance to heavy metals and the phage shock protein system via various Inc-type plasmids. Although few, there were still rare ST11_KL64_Taiwan strains that have evolved into hypervirulent CRKP through the horizontal acquisition of pLVPK variants. Comprehensive characterization of the high-risk ST11_KL64 lineage in Taiwan not only sheds light on its epidemic success but also provides essential data for ongoing surveillance efforts aimed at tracking the spread and evolution of ST11_KL64 across different geographical regions. Understanding the molecular underpinnings of CRKP evolution is crucial for developing effective strategies to combat its emergence and dissemination.
Regulatory T (Treg) cells are essential for maintaining immune homeostasis. Although Foxp3 expression marks the commitment of progenitors to Treg cell lineage, how Treg cells are generated during ...lymphocyte development remains enigmatic. We report here that the c-Rel transcription factor controlled development of Treg cells by promoting the formation of a
Foxp3-specific enhanceosome. This enhanceosome contained c-Rel, p65, NFAT, Smad, and CREB. Although Smad and CREB first bound to
Foxp3 enhancers, they later moved to the promoter to form the c-Rel enhanceosome. c-Rel-deficient mice had up to 90% reductions of Treg cells compared to wild-type mice, and c-Rel-deficient T cells were compromised in Treg cell differentiation. Thus, Treg cell development is controlled by a c-Rel enhanceosome, and strategies targeting Rel-NF-κB can be effective for manipulating Treg cell function.
CG23-I lineage constitutes the majority of hypervirulent Klebsiella pneumoniae. A diabetic patient suffered six episodes of infections caused by CG23-I K. pneumoniae. A total of nine isolates were ...collected in 2020. We performed whole-genome sequencing to elucidate the within-patient evolution of CG23-I K. pneumoniae. The maximum pairwise difference among the nine longitudinally collected isolates was five single nucleotide polymorphisms. One of the mutations was at the Asp87 position of GyrA. Four indels were identified, including an initiator tRNAfMet duplication, a tRNAArg deletion, a 7-bp insertion, and a 22-bp deletion. All 9 isolates had the genomic features of CG23-I K. pneumoniae, a chromosome-borne ICE
, and a large virulence plasmid. The carriage of a complete set of genes for the biosynthesis of colibactin by ICE
gave the nine isolates an ability to cause DNA damage to RAW264.7 cells. Compared with the initial isolate, the last isolate with an additional copy of initiator tRNA
grew faster in a nutrient-limiting condition and exhibited enhanced virulence in BALB/c mice. Collectively, we characterized the within-patient microevolution of CG23-I K. pneumoniae through an in-depth comparison of genome sequences. Using the
experiments and mouse models, we also demonstrated that these genomic alterations endowed the isolates with advantages to pass through
selection.
CG23-I is a significant lineage of hypervirulent Klebsiella pneumoniae. This study characterizes the within-patient microevolution of CG23-I K. pneumoniae. Selective pressures from continuous use of antibiotics favored point mutations contributing to bacterial resistance to antibiotics. The duplication of an initiator tRNA
gene helped CG23-I K. pneumoniae proliferate to reach a maximal population size during infections. For longer persistence inside a human host, the large virulence plasmid evolved with more flexible control of replication through duplication of the iteron-1 region. With the genomic alterations, the last isolate had a growth advantage over the initial isolate and exhibited enhanced virulence in BALB/c mice. This study gives us a deeper understanding of the genome evolution during the within-patient pathoadaptation of CG23-I K. pneumoniae.
A simple, low-cost, single-longitudinal mode, C-band narrow-linewidth optical fiber laser is presented based on the methodology of the Rayleigh backscattering (RBS). In this paper, a 1551 nm fiber ...ring laser is developed, and single-mode fiber (SMF) is added to compress the line width. When the SMF length of the RBS cavity is 120 m, the laser has better performance than that in other SMF lengths with a laser line width of 1.46 KHz with housing shield. The optical signal-to-noise ratio (OSNR) is 59.86 dB, and its maximum output power is 9.4 mW. It can quickly achieve the single longitude-mode operation by controlling the variable optical attenuator (VOA). The bit error rate at 10 Gb/s PRBS NRZ modulation is measured to be 10−9 when the optical receiving power is −16.2 dBm.
Current methods of fabric dyeing have a significant negative effect on the environment via toxic effluent emissions, high water usage, and high energy consumption. We demonstrate, for the first time, ...low-energy inkjet printing of an ecofriendly and biodegradable pigment derived from widely available spalting fungi with synthesis by-products that are fully biodegradable. Vivid and stable coloration is achieved on polyester and cotton using benign acetone-based and ethanol-based biopigment inks, with no liquid effluent or runoff, and without any synthetic dyes or mordants. We investigate the influence of fabric type, solvent type, and the number of printing passes on the color type, intensity, and uniformity, pigment crystallization, and environmental stability. Greater spatial definition of the printed pigment in inkjet printing effects greater crystallization and more vivid and uniform coloration as compared to drop-casting, the primary method used till date to color fabrics with such fungal biopigments. pH-driven interactions between the fabric, solvent, and biopigment cause solvent-driven changes in color type (from bluish to reddish) and fabric-governed changes in color intensity. The impact of our findings on minimizing the environmental impact of fabric dyeing is discussed.
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