15 research outputs found
Recent Advances in Divergent Synthetic Strategies for Indole-Based Natural Product Libraries
Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content screening (HCS) has emerged as a powerful tool in the development of novel therapeutic agents. Herein, we review the recent advances in divergent synthetic approaches such as complexity-to-diversity (Ctd) and biomimetic strategies for the generation of structurally complex and diverse indole-based natural product and natural product-like small-molecule libraries
Flow Cytometry-Based Quantification of Cellular Au Nanoparticles
There
has been a great deal of research regarding the cellular
association of nanoparticles (NPs), although there are only a few
methods available yet for the quantitative measurements of cellular
NPs. In this study, we propose a simple and quantitative method to
estimate the cellular uptake of Au NPs into cervical cancer cells
(HeLa) based on their side scattering (SSC) intensities measured by
flow cytometry (FCM). We have compared SSC intensities of HeLa cells
exposed to eight different types of Au NPs (40–100 nm size,
with positive or negative surface charge) with the amount of cellular
Au NPs measured by inductively coupled plasma mass spectrometry (ICPMS).
On the basis of these comparisons, we have found linear correlations
between the cellular Au NPs and the SSC intensities and used them
to estimate the amount of Au NPs associated with HeLa cells. Once
the correlations were found for specific cell lines and types of nanoparticles,
this approach is useful for simple and quantitative estimation of
the cellular Au NPs, without performing labor-intensive and complicated
sample preparation procedures required for the ICPMS approach
Identification and Characterization of a Novel, Cold-Adapted d-Xylobiose- and d-Xylose-Releasing Endo-β-1,4-Xylanase from an Antarctic Soil Bacterium, Duganella sp. PAMC 27433
Endo-β-1,4-xylanase is a key enzyme in the degradation of β-1,4-d-xylan polysaccharides through hydrolysis. A glycoside hydrolase family 10 (GH10) endo-β-1,4-xylanase (XylR) from Duganella sp. PAMC 27433, an Antarctic soil bacterium, was identified and functionally characterized. The XylR gene (1122-bp) encoded an acidic protein containing a single catalytic GH10 domain that was 86% identical to that of an uncultured bacterium BLR13 endo-β-1,4-xylanase (ACN58881). The recombinant enzyme (rXylR: 42.0 kDa) showed the highest beechwood xylan-degrading activity at pH 5.5 and 40 °C, and displayed 12% of its maximum activity even at 4 °C. rXylR was not only almost completely inhibited by 5 mM N-bromosuccinimide or metal ions (each 1 mM) including Hg2+, Ca2+, or Cu2+ but also significantly suppressed by 1 mM Ni2+, Zn2+, or Fe2+. However, its enzyme activity was upregulated (>1.4-fold) in the presence of 0.5% Triton X-100 or Tween 80. The specific activities of rXylR toward beechwood xylan, birchwood xylan, oat spelts xylan, and p-nitrophenyl-β-d-cellobioside were 274.7, 103.2, 35.6, and 365.1 U/mg, respectively. Enzymatic hydrolysis of birchwood xylan and d-xylooligosaccharides yielded d-xylose and d-xylobiose as the end products. The results of the present study suggest that rXylR is a novel cold-adapted d-xylobiose- and d-xylose-releasing endo-β-1,4-xylanase
Enhanced Immunogenic Cell Death by Apoptosis/Ferroptosis Hybrid Pathway Potentiates PD-L1 Blockade Cancer Immunotherapy
Even though chemotherapy regimens for treating cancer
by inducing
apoptosis are extensively utilized, their therapeutic effect is hindered
by multiple limitations. Thus, a combination of other types of anticancer
modalities is urgently needed. Herein, a tannic acid (TA)-Fe3+-coated doxorubicin (DOX)-encapsulated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene
glycol))-2000] (ammonium salt) (DSPE-PEG) micelle (TFDD) for apoptosis/ferroptosis-mediated
immunogenic cell death (ICD) is reported. By coating TA-Fe3+ on the surface of DOX-loaded micelles, an apoptotic agent and a
ferroptotic agent are simultaneously delivered into the cancer cells
and induce cell death. Furthermore, the intracellular oxidative environment
generated by the apoptosis/ferroptosis hybrid pathway stimulates the
endoplasmic reticulum (ER) and leads to ICD induction. The in vivo
results show that the combination treatment of TFDD and anti-programmed
death-ligand 1 antibodies (anti-PD-L1) considerably inhibits tumor
growth and improves antitumor immunity by activating CD4+ and CD8+ T cells and decreasing the ratio of regulatory
T cells (Treg) to CD4+ T cells. This study suggests that
the apoptosis/ferroptosis-mediated ICD inducer may offer a potent
strategy for enhanced cancer immunotherapy
Prediction of visual field from swept-source optical coherence tomography using deep learning algorithms
Engineering a tunable micropattern‐array assay to sort single extracellular vesicles and particles to detect RNA and protein in situ
Abstract The molecular heterogeneity of extracellular vesicles (EVs) and the co‐isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single‐EV and particle (siEVP) protein and RNA assay (siEVPPRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVPPRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single‐particle resolution, the siEVPPRA outperformed the sensitivities of bulk‐analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex biofluids, EVs from various glioma cell lines were processed with small RNA sequencing, whereby two mRNAs and two miRNAs associated with glioblastoma multiforme (GBM) were chosen for cross‐validation. Despite the presence of single‐EV‐LP co‐isolates in serum, the siEVPPRA detected GBM‐associated vesicular RNA profiles in GBM patient siEVPs. The siEVPPRA effectively examines intravesicular, intervesicular, and interparticle heterogeneity with diagnostic promise
Do board directors affect the export propensity and export performance of Korean firms? A resource dependence perspective
Using the Heckman two-stage method, this study empirically investigates whether board directors’ work experience in government and multinational corporations (MNCs), as well as the proportion of outside directors affects export propensity and export performance based on a sample of Korean firms. We find that the Korean firms with former government officials on the board are more likely to engage in exporting, although there is no empirical evidence supporting export performance. The findings also show that firms with former MNC employees on the board demonstrate higher levels of export propensity and export performance. Similarly, firms with a higher proportion of outside directors exhibit a higher level of export propensity and export performance. These findings highlight the importance of the board of directors in Korean firms’ first stage of internationalization and provide new insights into which type of board members can benefit their firms in terms of export propensity and export performance
Relationship between corneal biomechanical properties and structural biomarkers in patients with normal-tension glaucoma: a retrospective study
ILC Reference Design Report Volume 1 - Executive Summary
The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization