597 research outputs found
Clinical significance and therapeutic value of glutathione peroxidase 3 (GPx3) in hepatocellular carcinoma
AIMS:
We aimed to investigate the clinical significance of GPx3 in hepatocellular carcinoma (HCC) and to characterize its tumor suppressive role.
METHODS:
HCC patients (113) who underwent hepatectomy were recruited to examine the clinical relevance of GPx3. The tumor suppressive role of GPx3 was studied by administration of recombinant GPx3 (rGPx3) or over-expression of GPx3 in HCC cells in vitro and in vivo. The therapeutic value of GPx3 for HCC was further investigated using human induced pluripotent stem cell derived mesenchymal stem cells (hiPSC-MSCs) as its delivery vehicle.
RESULTS:
Down-regulation of GPx3 significantly correlated with advanced tumor stage (P = 0.024), venous infiltration (P = 0.043) and poor overall survival (P = 0.007) after hepatectomy. Lower plasma GPx3 in HCC patients was significantly associated with larger tumor size (P = 0.011), more tumor nodules (P = 0.032) and higher recurrence (P = 0.016). Over-expression of GPx3 or administration of rGPx3 significantly inhibited proliferation and invasiveness of HCC cells in vitro and in vivo. Tumor suppressive activity of GPx3 was mediated through Erk-NFκB-SIP1 pathway. GPx3 could be delivered by hiPSC-MSCs into the tumor and exhibited tumor suppressive activity in vivo.
CONCLUSIONS:
GPx3 is a tumor suppressor gene in HCC and may possess prognostic and therapeutic value for HCC patients.published_or_final_versio
Interrogating Institutionalized Establishments: Urban-Rural Inequalities in China’s Higher Education
postprin
Waterproof Flexible InP@ZnSeS Quantum Dot Light-Emitting Diode
The development of flexible displays for wearable electronics applications has created
demand for high-performance quantum dot (QD) light-emitting diodes (QLEDs) based on QD
core@shell structures. Emerging indium phosphide (InP)-based core@shell QDs show
promise as lighting material in the field of optoelectronics because they are environmentally
friendly material, can be produced in a cost-effective manner, and are capable of tunable
emission. While efforts have been made to enhance the performance of InP-based QLED, the
stabilities of InP@ZnSeS QDs film and InP@ZnSeS-based QLED in water/air are not yet
fully understood, limiting their practical applications. Herein, a highly durable, flexible
InP@ZnSeS QLED encapsulated in an ultrathin film of CYTOP, a solution-based amorphous
fluoropolymer, is demonstrated. The CYTOP-encapsulated green flexible QLED shows an
external quantum efficiency (EQE) of 0.904% and a high luminescence of 1593 cd/m2
as
well as outstanding waterproof performance. The flexible device emits strong luminescence
after being immersed in water for ~20 minutes. Even when subjected to continuous tensile
stress with a 5 mm bending radius, the high luminescence is preserved. This waterproof
architecture can be a promising strategy for wearable electronics applications
Quantifying Inactive Lithium in Lithium Metal Batteries
Inactive lithium (Li) formation is the immediate cause of capacity loss and
catastrophic failure of Li metal batteries. However, the chemical component and
the atomic level structure of inactive Li have rarely been studied due to the
lack of effective diagnosis tools to accurately differentiate and quantify Li+
in solid electrolyte interphase (SEI) components and the electrically isolated
unreacted metallic Li0, which together comprise the inactive Li. Here, by
introducing a new analytical method, Titration Gas Chromatography (TGC), we can
accurately quantify the contribution from metallic Li0 to the total amount of
inactive Li. We uncover that the Li0, rather than the electrochemically formed
SEI, dominates the inactive Li and capacity loss. Using cryogenic electron
microscopies to further study the microstructure and nanostructure of inactive
Li, we find that the Li0 is surrounded by insulating SEI, losing the electronic
conductive pathway to the bulk electrode. Coupling the measurements of the Li0
global content to observations of its local atomic structure, we reveal the
formation mechanism of inactive Li in different types of electrolytes, and
identify the true underlying cause of low Coulombic efficiency in Li metal
deposition and stripping. We ultimately propose strategies to enable the highly
efficient Li deposition and stripping to enable Li metal anode for next
generation high energy batteries
Overexpression of Nrdp1 in the Heart Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice
BACKGROUND: Cardiac cell death and generation of oxidative stress contribute to doxorubicin (DOX)-induced cardiac dysfunction. E3 ligase Nrdp1 plays a critical role in the regulation of cell apoptosis, inflammation and production of reactive oxygen species (ROS), which may contribute to heart failure. However, the role of Nrdp1 in DOX-induced cardiac injury remains to be determined. METHODS AND RESULTS: We examined the effect of Nrdp1 overexpression with DOX treatment in rat neonatal cardiomyocytes and mouse heart tissue. Cardiomyocytes were infected with adenovirus containing GFP (Ad-GFP), Nrdp1 wild-type (Ad-Nrdp1) or the dominant-negative form of Nrdp1 (Ad-Dn-Nrdp1), then treated with DOX for 24 hr. DOX treatment increased cell death and apoptosis, with Ad-Nrdp1 infection enhancing these actions but Ad-Dn-Nrdp1 infection attenuating these effects. Furthermore, 5 days after a single injection of DOX (20 mg/kg, intraperitoneally), Nrdp1 transgenic mice (TG) showed decreased cardiac function and increased apoptosis, autophagy and oxidative stress as compared with wild-type (WT) mice (P<0.01). Survival rate was significantly lower in Nrdp1 TG mice than in WT mice 10 days after DOX injection (P<0.01). CONCLUSIONS/SIGNIFICANCE: These results were associated with decreased activation of Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. Nrdp1 may be a key mediator in the development of cardiac dysfunction after DOX treatment and associated with inhibition of Akt, ERK1/2 and STAT3. Nrdp1 may be a new therapeutic target in protecting against the cardiotoxic effects of DOX
Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis
Cisplatin has been widely employed as a cornerstone chemotherapy treatment for a wide spectrum of solid neoplasms; increasing tumor responsiveness to cisplatin has been a topic of interest for the past 30 years. Strong evidence has indicated that mitochondrial fission participates in the regulation of apoptosis in many diseases; however, whether mitochondrial fission regulates cisplatin sensitivity remains poorly understood. Here, we show that MFF mediated mitochondrial fission and apoptosis in tongue squamous cell carcinoma (TSCC) cells after cisplatin treatment and that miR-593-5p was downregulated in this process. miR-593-5p attenuated mitochondrial fission and cisplatin sensitivity by targeting the 3’ untranslated region sequence of MFF and inhibiting its translation. In exploring the underlying mechanism of miR-593-5p downregulation, we observed that BRCA1 transactivated miR-593-5p expression and attenuated cisplatin sensitivity in vitro. The BRCA1-miR-593-5p-MFF axis also affected cisplatin sensitivity in vivo. Importantly, in a retrospective analysis of multiple centers, we further found that the BRCA1-miR-593-5p-MFF axis was significantly associated with cisplatin sensitivity and the survival of patients with TSCC. Together, our data reveal a model for mitochondrial fission regulation at the transcriptional and post-transcriptional levels; we also reveal a new pathway for BRCA1 in determining cisplatin sensitivity through the mitochondrial fission program.published_or_final_versio
CTLA4 is expressed on mature dendritic cells derived from human monocytes and influences their maturation and antigen presentation
<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) initiate immune responses through their direct interaction with effector cells. However, the mechanism by which DC activity is regulated is not well defined. Previous studies have shown that CTLA4 on T cells regulates DCs function by "cross-talk". We investigated whether there is an intrinsic regulatory mechanism in DCs, with CTLA4 as a candidate regulator.</p> <p>Results</p> <p>We confirmed via RT-PCR and flow cytometry the natural expression of CTLA4 on mature DCs derived from human monocytes. Approximately 8% CD1a-positive cells express CTLA4 both on surface and intracellular, whereas 10% CD1a-negative cells express CTLA4 intracellularly, but little expression was observed on the cell surface. The cross-linking of CTLA4 inhibits DCs maturation and antigen presentation in vitro, but does not inhibit endocytosis.</p> <p>Conclusions</p> <p>CTLA4 is expressed by DCs and plays an inhibitory role. CTLA4-expressing DCs may represent a group of regulatory DCs. Because of its wide distribution on different cell types, CTLA4 may play a general role in regulating immune responses.</p
Investigation on the Plasma-Induced Emission Properties of Large Area Carbon Nanotube Array Cathodes with Different Morphologies
Large area well-aligned carbon nanotube (CNT) arrays with different morphologies were synthesized by using a chemical vapor deposition. The plasma-induced emission properties of CNT array cathodes with different morphologies were investigated. The ratio of CNT height to CNT-to-CNT distance has considerable effects on their plasma-induced emission properties. As the ratio increases, emission currents of CNT array cathodes decrease due to screening effects. Under the pulse electric field of about 6 V/μm, high-intensity electron beams of 170–180 A/cm2 were emitted from the surface plasma. The production mechanism of the high-intensity electron beams emitted from the CNT arrays was plasma-induced emission. Moreover, the distribution of the electron beams was in situ characterized by the light emission from the surface plasma
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