Epithelial-mesenchymal transition (EMT), a critical process of cancer invasion and metastasis, is associated with stemness property of cancer cells. Though Oct4 and Nanog are homebox transcription ...factors essential to the self-renewal of stem cells and are expressed in several cancers, the role of Oct4/Nanog signaling in tumorigenesis is still elusive. Here microarray and quantitative real-time PCR analysis showed a parallel, elevated expression of Oct4 and Nanog in lung adenocarcinoma (LAC). Ectopic expressions of Oct4 and Nanog in LACs increased the percentage of CD133-expressing subpopulation and sphere formation, enhanced drug resistance, and promoted EMT. Ectopic expressions of Oct4 and Nanog activated Slug and enhanced the tumor-initiating capability of LAC. Furthermore, double knockdown of Oct4 and Nanog suppressed the expression of Slug, reversed the EMT process, blocked the tumorigenic and metastatic ability, and greatly improved the mean survival time of transplanted immunocompromised mice. The immunohistochemical analysis demonstrated that expressions of Oct4, Nanog, and Slug were present in high-grade LAC, and triple positivity of Oct4/Nanog/Slug indicated a worse prognostic value of LAC patients. Our results support the notion that the Oct4/Nanog signaling controls epithelial-mesenchymal transdifferentiation, regulates tumor-initiating ability, and promotes metastasis of LAC.
MRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver-specific contrast agents which enhance lesions in T
-weighted images. Iron oxide ...nano-particle m-PEG-silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial.
To evaluate the safety and clinical validity of IOP Injection as MRI contrast agent in diagnosing HCC.
Prospective.
A total of 52 subjects (61.6 ± 11.05 years, 45 males/7 females) with suspected HCC.
1.5 T, T
-weighted in/opposed phase, T
*-weighted gradient echo, T
-weighted fast spin echo, true fast imaging with steady-state free precession.
Adverse effects and clinical monitoring were recorded throughout the 5-day study. Two independent readers (M.G.H. with 30 years of experience, S.P.K. with 26 years of experience) made the diagnosis. The diagnostic performance of IOP-enhanced MRI was evaluated with sensitivity and positive predictive value by comparing to the pathology reports from subsequent hepatic resection. The number of lesions with various sizes and degrees of differentiation detected by IOP-enhanced MRI was assessed. The relative change in signal intensities over time was indirectly measured from acquired images.
Sensitivity and positive predictive value were used to evaluate the diagnostic performance of IOP-enhanced MRI. Prevalence-adjusted and bias-adjusted 𝜅 coefficient was used to assess the interreader variability.
No serious adverse event related to IOP Injection was found. IOP Injection enhanced the lesion-to-liver contrast ratio in T
*-weighted images by 50.1% ± 4.8%. IOP-enhanced MRI detected HCC with 100% sensitivity by subject and 96% sensitivity by lesion. IOP Injection visualized subtle vascular invasion as filling defect within vessels in true fast imaging with steady-state free precession (TrueFISP) images.
IOP Injection was safe and efficacious as MRI contrast agent in diagnosing HCC in a limited group of subjects.
2.
Stage 2.
Summary
Thiamin diphosphate (TPP, vitamin B1) is an essential coenzyme present in all organisms. Animals obtain TPP from their diets, but plants synthesize TPPde novo. We isolated and characterized ...an Arabidopsis pale green1 (pale1) mutant that contained higher concentrations of thiamin monophosphate (TMP) and less thiamin and TPP than the wild type. Supplementation with thiamin, but not the thiazole and pyrimidine precursors, rescued the mutant phenotype, indicating that the pale1 mutant is a thiamin‐deficient mutant. Map‐based cloning and whole‐genome sequencing revealed that the pale1 mutant has a mutation in At5g32470 encoding a TMP phosphatase of the TPP biosynthesis pathway. We further confirmed that the mutation of At5g32470 is responsible for the mutant phenotypes by complementing the pale1 mutant with constructs overexpressing full‐length At5g32470. Most plant TPP biosynthetic enzymes are located in the chloroplasts and cytosol, but At5g32470‐GFP localized to the mitochondrion of the root, hypocotyl, mesophyll and guard cells of the 35S:At5g32470‐GFP complemented plants. The subcellular localization of a functional TMP phosphatase suggests that the complete vitamin B1 biosynthesis pathway may involve the chloroplasts, mitochondria and cytosol in plants. Analysis of PALE1 promoter‐uidA activity revealed that PALE1 is mainly expressed in vascular tissues of Arabidopsis seedlings. Quantitative RT‐PCR analysis of TPP biosynthesis genes and genes encoding the TPP‐dependent enzymes pyruvate dehydrogenase, α‐ketoglutarate dehydrogenase and transketolase revealed that the transcript levels of these genes were upregulated in the pale1 mutant. These results suggest that endogenous levels of TPP may affect the expression of genes involved in TPP biosynthesis and TPP‐dependent enzymes.
Significance Statement
Arabidopsis PALE1 encodes a thiamin monophosphate phosphatase that localizes in the mitochondria. The complete vitamin B1 biosynthesis pathway may involve the chloroplasts, mitochondria and cytosol.
Aims and objectives
To determine factors associated with nurses’ spiritual care competencies.
Background
Holistic nursing care includes biopsychosocial and spiritual care. However, nurses are limited ...by a lack of knowledge, time constraints and apprehension of assessing spiritual issues, which leaves them unable to assess and meet patients’ spiritual needs. Thus, when patients experience spiritual distress, clinical nurses lose the opportunity to support spiritual growth and self‐actualisation. In Taiwan, spiritual care, religion and culture are unique compared to those in other countries. Overall, factors associated with Taiwanese nurses’ spiritual care competencies lack comprehensive exploration.
Methods
This study adopted a descriptive correlational design using cross‐sectional survey (see Appendix S1). Cluster sampling was used to select clinical nurses from fourteen units of a medical centre and a regional hospital. Data were collected from January–June 2018 with a 97.03% response rate. Clinical nurses completed a background questionnaire, spiritual care practice questionnaire, spirituality and spiritual care‐related scales. Data were analysed using descriptive and linear regression. This report followed the STROBE checklist.
Results
Spiritual care competence ranged from 44–123 (mean 84.67 ± 12.88; range 27–135). The majority of clinical nurses rated their spiritual care competence as moderate (64–98). The significant factors associated with nurses’ spiritual care competence were education, religion, interest in spiritual care, having role models, past life events, barriers to providing spiritual care of the spiritual care practice score, and spiritual attitude and involvement score. The overall model was significant (p < .001) and accounted for 55.0% of variance (adjusted R2 = .488).
Conclusions
Most clinical nurses have moderate spiritual care competence. Objective factors identified affect clinical nurses’ spiritual care competencies.
Relevance to clinical practice
To improve nurses’ spiritual care competencies, objective factors that affect clinical nurses’ spiritual care competencies must be emphasised. Multiple strategies for enhancing nurses’ own spiritual well‐being can be provided via employee health promotion projects and activities, and promoting nurses’ spirituality and spiritual care competencies can be explored in clinical settings through bedside teaching, situational simulation, objective structured clinical examinations and self‐reflection.
While immunotherapy has emerged as a promising strategy to treat glioblastoma multiforme (GBM), the limited availability of immunotherapeutic agents in tumors due to the presence of the blood–brain ...barrier (BBB) and immunosuppressive tumor microenvironment dampens efficacy. Nitric oxide (NO) plays a role in modulating both the BBB and tumor vessels and could thus be delivered to disrupt the BBB and improve the delivery of immunotherapeutics into GBM tumors. Herein, we report an immunotherapeutic approach that utilizes CXCR4-targeted lipid‑calcium-phosphate nanoparticles with NO donors (LCP-NO NPs). The delivery of NO resulted in enhanced BBB permeability and thus improved gene delivery across the BBB. CXCR4-targeted LCP-NO NPs delivered siRNA against the immune checkpoint ligand PD-L1 to GBM tumors, silenced PD-L1 expression, increased cytotoxic T cell infiltration and activation in GBM tumors, and suppressed GBM progression. Thus, the codelivery of NO and PD-L1 siRNA by these CXCR4-targeted NPs may serve as a potential immunotherapy for GBM.
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Followed by the fast developments in Internet of Things (IoT), artificial intelligence (AI) technologies, utilizing cloud architecture and big data, have been integrated into various aspects of our ...daily lives. Such an integration results in high levels of convenience, comfort, and energy savings. Deploying such new technologies benefits the elevator industry as well. Intelligent elevator with energy control schemes can improve the energy efficiency of eco-friendly applications. The purpose of this study is to examine the factors that affect the intelligent elevator adoption of Taiwanese people using the extended unified theory of acceptance and use of technology (UTAUT 2) model, which considers factors such as environmental consciousness, artificial intelligence optimism, attitude, and perceived quality. A well-structured face-to-face survey is performed to obtain data from the consumers living in central Taiwan. The data acquired are analyzed via structural equation modeling using the partial least squares method. The analysis results indicate that attitude, habit, performance expectancy, effort expectancy, and perceived quality are important factors that affect the behavioral intentions of consumers when adopting new technologies, such as an intelligent elevator. However, facilitating conditions adversely affect the behavioral intentions. In addition, environmental consciousness and artificial intelligence optimism are crucial factors that affect performance and effort expectancies, whereas the latter two contribute positively to attitude. The findings of this study supplement existing literature regarding the behavioral intentions for adopting intelligent elevators. Finally, the theoretical and practical significances of this research study are discussed.
•The optimal culture medium of Photorhabdus luminescens significantly increases insecticidal activity against Plutella xylostella.•Ph. luminescens can accelerate the insecticidal effect of Bacillus ...thuringiensis against Plutella xylostella.
Plutella xylostella is a major pest of cruciferous vegetables worldwide. We evaluated a biopesticide using different culture treatments of Photorhabdus luminescens (ATCC 29,999) and Bacillus thuringiensis subsp. aizawai and examined their insecticidal activity against Pl. xylostella.
L8 and L9 Taguchi orthogonal designs were adopted to evaluate the optimal culture medium for enhanced insecticidal activity. Feeding bioassays were conducted to determine the potential synergistic effects of combining B. thuringiensis and Ph. luminescens, and the most effective synergistic combination was identified by analyzing the time–mortality response against Pl. xylostella.
Analysis of the pH value indicates that Ph. luminescens has enhanced tolerance to acidic conditions and can alkalize the medium. Among the various medium combinations, Ph. luminescens optimized using A3B1C3N2—d10 × concentration, 24-h cultivation time, 1.25 % molasses as the carbon source, and a nitrogen source consisting of yeast extract powder, yeast powder, and amino acids (0.2:0.3:0.5 %)—resulted in the highest insect mortality. Synergistic interactions between B. thuringiensis and Ph. luminescens were observed in the 1:1 mixture, likely due to immune system suppression. These results highlight the potential of combining Ph. luminescens and B. thuringiensis to prepare a potent bioinsecticide against Pl. xylostella and other lepidopteran pests, thereby decreasing the reliance on chemical pesticides.
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Thiamin diphosphate (TPP, vitamin B
) is an essential coenzyme present in all organisms. Animals obtain TPP from their diets, but plants synthesize TPPde novo. We isolated and characterized an ...Arabidopsis pale green1 (pale1) mutant that contained higher concentrations of thiamin monophosphate (TMP) and less thiamin and TPP than the wild type. Supplementation with thiamin, but not the thiazole and pyrimidine precursors, rescued the mutant phenotype, indicating that the pale1 mutant is a thiamin-deficient mutant. Map-based cloning and whole-genome sequencing revealed that the pale1 mutant has a mutation in At5g32470 encoding a TMP phosphatase of the TPP biosynthesis pathway. We further confirmed that the mutation of At5g32470 is responsible for the mutant phenotypes by complementing the pale1 mutant with constructs overexpressing full-length At5g32470. Most plant TPP biosynthetic enzymes are located in the chloroplasts and cytosol, but At5g32470-GFP localized to the mitochondrion of the root, hypocotyl, mesophyll and guard cells of the 35S:At5g32470-GFP complemented plants. The subcellular localization of a functional TMP phosphatase suggests that the complete vitamin B1 biosynthesis pathway may involve the chloroplasts, mitochondria and cytosol in plants. Analysis of PALE1 promoter-uidA activity revealed that PALE1 is mainly expressed in vascular tissues of Arabidopsis seedlings. Quantitative RT-PCR analysis of TPP biosynthesis genes and genes encoding the TPP-dependent enzymes pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase revealed that the transcript levels of these genes were upregulated in the pale1 mutant. These results suggest that endogenous levels of TPP may affect the expression of genes involved in TPP biosynthesis and TPP-dependent enzymes.
Nitric oxide (NO),
a pro-neurogenic and antineuroinflammatory gasotransmitter,
features the potential to develop a translational medicine against
neuropathological conditions. Despite the extensive ...efforts made on
the controlled delivery of therapeutic NO, however, an orally active
NO prodrug for a treatment of chronic neuropathy was not reported
yet. Inspired by the natural dinitrosyl iron unit (DNIU) Fe(NO)
2
, in this study, a reversible and dynamic interaction between
the biomimetic (NO)
2
Fe(μ-SCH
2
CH
2
OH)
2
Fe(NO)
2
(
DNIC-1
) and serum
albumin (or gastrointestinal mucin) was explored to discover endogenous
proteins as a vehicle for an oral delivery of NO to the brain after
an oral administration of
DNIC-1
. On the basis of the
in vitro and in vivo study, a rapid binding of
DNIC-1
toward gastrointestinal mucin yielding the mucin-bound dinitrosyl
iron complex (DNIC) discovers the mucoadhesive nature of
DNIC-1
. A reversible interconversion between mucin-bound DNIC and
DNIC-1
facilitates the mucus-penetrating migration of
DNIC-1
shielded in the gastrointestinal tract of the stomach
and small intestine. Moreover, the NO-release reactivity of
DNIC-1
induces the transient opening of the cellular tight
junction and enhances its paracellular permeability across the intestinal
epithelial barrier. During circulation in the bloodstream, a stoichiometric
binding of
DNIC-1
to the serum albumin, as another endogenous
protein vehicle, stabilizes the DNIU Fe(NO)
2
for a subsequent
transfer into the brain. With aging mice under a Western diet as a
disease model for metabolic syndrome and cognitive impairment, an
oral administration of
DNIC-1
in a daily manner for 16
weeks activates the hippocampal neurogenesis and ameliorates the impaired
cognitive ability. Taken together, these findings disclose the synergy
between biomimetic
DNIC-1
and endogenous protein vehicles
for an oral delivery of therapeutic NO to the brain against chronic
neuropathy.
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