10 research outputs found
The impacts of consumer value and brand identification on brand loyalty and electronic word of mouth: the case of smartphone market in Ho Chi Minh City
Finding out the antecedents of brand loyalty is an interesting topic. The paper’s target is
answering the question “Do consumer value and consumer-brand identification lead to
consumer’s loyalty with the brand and positive electronic word of mouth in the context of
smartphone market in Ho Chi Minh City?”. The authors used the PLS-SEM (Partial least
squares structural equation modeling) to verify the relationship between independent variables
and dependent variables using data collected from 320 smartphone users. The study shows
that proposed antecedents have influences on dependent constructs. Such discoveries have
both theoretical and practical implications. In theory, they support the theory of consumer
value and the approach of brand identification. In practice, smartphone producers should
provide gadgets with excellent performance and unique identity to keep consumers’ loyalty.
As a result, companies will have active ambassadors for their brand
Multifunctional engineering on the ultrasensitive driven-dual plasmonic heterogenous dimer system of 1D semiconductor for accurate SERS sensitivity and quantitation
Self-assembled functional nanomaterials with electromagnetic (EM) hot spots and chemical (CM) enhancement have been recognized as a key in surface-enhanced Raman scattering (SERS) analysis. Herein, a dual-hybrid plasmonic coupling SERS sensor composed of rutile TiO2 nanorod arrays (r-TNRs), Au nanospheres (AuNSs), and Ag nanocubes (AgNCs) has been designed to achieve ultrasensitive detection and obtain unique molecular fingerprints. The AgNCs/AuNSs/r-TNRs-based SERS chip shows an extremely promising SERS enhancement factor (EF) of 1.2 ×1011, detectability at sub-picomolar concentrations (down to the single-molecule level, 10-13 M), and excellent signal reproducibility with a relative standard deviation (RSD) of 3.4 %. Furthermore, this system has been applied for fingerprint detection in complex mixtures, demonstrating impressive specificity and accuracy. The photocatalytic decomposition efficiency of the AgNCs/AuNSs/r-TNRs platform reaches approximately ∼99 % within 20 min. Additionally, the Raman intensity of crystal violet only declined by 15 % after 21 days, illustrating the outstanding stability of the as-proposed ternary SERS sensor
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Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor
The bromodomain containing proteins
TRIM24 (tripartite motif containing
protein 24) and BRPF1 (bromodomain and PHD finger containing protein
1) are involved in the epigenetic regulation of gene expression and
have been implicated in human cancer. Overexpression of TRIM24 correlates
with poor patient prognosis, and BRPF1 is a scaffolding protein required
for the assembly of histone acetyltransferase complexes, where the
gene of MOZ (monocytic leukemia zinc finger protein) was first identified
as a recurrent fusion partner in leukemia patients (8p11 chromosomal
rearrangements). Here, we present the structure guided development
of a series of <i>N</i>,<i>N</i>-dimethylbenzimidazolone
bromodomain inhibitors through the iterative use of X-ray cocrystal
structures. A unique binding mode enabled the design of a potent and
selective inhibitor <b>8i</b> (IACS-9571) with low nanomolar
affinities for TRIM24 and BRPF1 (ITC <i>K</i><sub>d</sub> = 31 nM and ITC <i>K</i><sub>d</sub> = 14 nM, respectively).
With its excellent cellular potency (EC<sub>50</sub> = 50 nM) and
favorable pharmacokinetic properties (<i>F</i> = 29%), <b>8i</b> is a high-quality chemical probe for the evaluation of
TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo
MOESM1 of Development of novel cellular histone-binding and chromatin-displacement assays for bromodomain drug discovery
Additional file 1. Six supplementary figures and three supplementary tables
Functional Genomics Reveals Synthetic Lethality between Phosphogluconate Dehydrogenase and Oxidative Phosphorylation
Summary: The plasticity of a preexisting regulatory circuit compromises the effectiveness of targeted therapies, and leveraging genetic vulnerabilities in cancer cells may overcome such adaptations. Hereditary leiomyomatosis renal cell carcinoma (HLRCC) is characterized by oxidative phosphorylation (OXPHOS) deficiency caused by fumarate hydratase (FH) nullizyogosity. To identify metabolic genes that are synthetically lethal with OXPHOS deficiency, we conducted a genetic loss-of-function screen and found that phosphogluconate dehydrogenase (PGD) inhibition robustly blocks the proliferation of FH mutant cancer cells both in vitro and in vivo. Mechanistically, PGD inhibition blocks glycolysis, suppresses reductive carboxylation of glutamine, and increases the NADP+/NADPH ratio to disrupt redox homeostasis. Furthermore, in the OXPHOS-proficient context, blocking OXPHOS using the small-molecule inhibitor IACS-010759 enhances sensitivity to PGD inhibition in vitro and in vivo. Together, our study reveals a dependency on PGD in OXPHOS-deficient tumors that might inform therapeutic intervention in specific patient populations. : Loss-of-function genetics screen reveals a synthetically lethal interaction between OXPHOS inhibition and phosphogluconate dehydrogenase (PGD) inactivation. Sun et al. provide an example of targeting tumor metabolism in a genetically predefined context to maximize therapeutic impact and propose PGD as a therapeutic target for fumarate hydratase-deficient HLRCC. Keywords: synthetic lethality, PGD, OXPHOS, tumor metabolism, metabolic vulnerability, fumarate hydratase, redox homeostasis, functional genomics, hereditary leiomyomatosis renal cell carcinoma, pentose phosphate pathwa