Single phase PbHfO3 antiferroelectric ceramics were prepared via rolling process. It is revealed that the rolling process can reduce the grain size and increase the bulk density, which lead to the ...enhanced breakdown strength up to 268 kV/cm versus 219 kV/cm of samples using the conventional solid-state method. As a result, high recoverable energy density of 7.6 J/cm3 with an efficiency of 80.8 % was achieved. Meanwhile, a large current density of 1381 A/cm2 and an ultrahigh peak power density up to 170 MW/cm3 were observed under 250 kV/cm. In addition, unique electrical polarization response characteristics at different electric fields and temperature-induced structural phase transitions were also investigated. The energy storage performance and charge-discharge properties of PbHfO3 were first studied in this communication and all the results indicate that PbHfO3 ceramic is a promising candidate for pulse power applications.
Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical ...regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.
What's new?
Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating tumor malignant properties within the tumor microenvironment. However, the role of CAFs in tumor PD‐L1 expression and immune evasion in melanoma and colorectal carcinoma (CRC) is not completely understood. Here, the authors observe a positive correlation between CAFs and PD‐L1 expression in patients. CAFs promote PD‐L1 expression in tumor cells by secreting CXCL5 and in turn activating the PI3K/AKT signaling pathway. The findings reveal a complex tumor‐promoting microenvironment shaped by the CXCL5‐CXCR2 axis and highlight CAFs as a promising target to curb immune evasion.
Studies on biological functions of N
-methyladenosine (m
A) modification in mRNA have sprung up in recent years. We find m
A can positively regulate the glycolysis of cancer cells. Specifically, m
...A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m
A regulated glycolysis and ATP generation. The m
A modified 5'UTR of PDK4 positively regulates its translation elongation and mRNA stability via binding with YTHDF1/eEF-2 complex and IGF2BP3, respectively. Targeted specific demethylation of PDK4 m
A by dm
ACRISPR system can significantly decrease the expression of PDK4 and glycolysis of cancer cells. Further, TATA-binding protein (TBP) can transcriptionally increase the expression of Mettl3 in cervical cancer cells via binding to its promoter. In vivo and clinical data confirm the positive roles of m
A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m
A regulates glycolysis of cancer cells through PDK4.
•Comprehensive fluid-rock interaction models were built for CPG system study.•Back and down flow of water complicates fluid-rock interactions near injector.•Salt precipitation can affect geochemical ...reaction during geothermal development.•Geochemical reaction and salt precipitation reduce heat mining rate up to 2/5.•Low salinity water injection can effectively reduce salt precipitation in CPG.
The ubiquitous natural sedimentary reservoirs and their high permeability have made the CO2 plume geothermal system increasingly attractive. However, the complicated fluid-rock interactions during the geothermal exploitation can cause severe reservoir damage, constraining the excellent heat mining performance of the CO2 and decreasing the possible applications of the CO2 plume geothermal system. In order to analyze and solve this energy issue affecting the geothermal exploitation, in this study, a comprehensive numerical simulation model was established, which can consider formation water evaporation, salt precipitation, CO2-water-rock geochemical reactions, and the changes in reservoir porosity and permeability in the CO2 plume geothermal (CPG) system. Using this model, the geochemical reactions and salt precipitation and their effects on the geothermal exploitation were analyzed, and some measures were proposed to reduce the influence of fluid-rock interactions on the heat mining rate. The simulation results show that the gravity and the negative gas-liquid capillary pressure gradient induced by evaporation can cause the formation water to flow toward the injector. The back flow of the formation water results in salt precipitation accumulation in the injection well region, which can cause severe reservoir damage and consequent reductions to the heat mining rate. The CO2-water-rock geochemical reactions could result in the dissolution of certain minerals and precipitation of others, but its minimal influence on the heat mining rate can be ignored. However, salt precipitation can affect the geochemical reactions by influencing the CO2 flow and distribution, which can reduce the heat mining rate up to 2/5 of the original. Sensitivity studies show that the reservoir condition can affect the salt precipitation and heat mining rate, so a sedimentary reservoir with high temperature, high porosity and permeability, and low salinity should be selected for CPG application, with an appropriately high injection-production pressure difference. The injection of low salinity water before CO2 injection and the combined injection of CO2 and water vapor can be applied to reduce the salt precipitation and increase the heat mining rate in the CPG system.
Background Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified. ...Methods lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138 J23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed. Results RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m.sup.6A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m.sup.6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC. Conclusions m.sup.6A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC. Keywords: LncRNA RP11, CRC, Zeb1, m.sup.6A, hnRNPA2B1, Cell dissemination
Studies on biological functions of N6-methyladenosine (m6A) modification in mRNA have drawn significant attention in recent years. Here we describe the construction and characterization of a ...CRISPR-Cas13b-based tool for targeted demethylation of specific mRNA. A fusion protein, named dm6ACRISPR, was created by linking a catalytically inactive Type VI-B Cas13 enzyme from Prevotella sp. P5-125 (dPspCas13b) to m6A demethylase AlkB homolog 5 (ALKBH5). dm6ACRISPR specifically demethylates m6A of targeted mRNA such as cytochrome b5 form A (CYB5A) to increase its mRNA stability. It can also demethylate β-catenin-encoding CTNNB1 mRNA that contains multiple m6A sites to trigger its translation. In addition, the dm6ACRISPR system incurs efficient demethylation of targeted epitranscriptome transcripts with limited off-target effects. Targeted demethylation of transcripts coding for oncoproteins such as epidermal growth factor receptor (EGFR) and MYC can suppress proliferation of cancer cells. Together, we provide a programmable and in vivo manipulation tool to study mRNA modification of specific genes and their related biological functions.
Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N1-methyladenosine (m1A), which is dynamically regulated by writers, erasers and readers, has been found ...as a reversible modification in tRNA, mRNA, rRNA and long non-coding RNA (lncRNA). m1A modification has impacts on the RNA processing, structure and functions of targets. Increasing studies reveal the critical roles of m1A modification and its regulators in tumorigenesis. Due to the positive relevance between m1A and cancer development, targeting m1A modification and m1A-related regulators has been of attention. In this review, we summarized the current understanding of m1A in RNAs, covering the modulation of m1A modification in cancer biology, as well as the possibility of targeting m1A modification as a potential target for cancer diagnosis and therapy.
With the rise of the Internet of Things (IoT), the number of mobile devices with sensing and computing capabilities increases dramatically, paving the way toward an emerging paradigm, i.e., ...crowdsensing that facilitates the interactions between humans and the surrounding physical world. Despite its superiority, particular attention is paid to be able to submit sensing data to the platform wherever possible to avoid leaking the sensitive information of participants and to incentivize them to improve sensing quality. In this article, we propose an incentive mechanism for participants, aiming to protect them from privacy leakage, ensure the availability of sensing data, and maximize the utilities of both platforms and participants by means of distributing different sensing tasks to different participants. More specifically, we formulate the interactions between platforms and participants as a multileader-multifollower Stackelberg game and derive the Stackelberg equilibrium (SE) of the game. Due to the difficulty to obtain the optimal strategy, a reinforcement learning algorithm, i.e., <inline-formula> <tex-math notation="LaTeX">Q </tex-math></inline-formula>-learning is adopted to obtain the optimal sensing contributions of participants. In order to accelerate learning speed and reduce overestimation, a deep learning algorithm combined with <inline-formula> <tex-math notation="LaTeX">Q </tex-math></inline-formula>-learning in a dueling network architecture, i.e., double deep <inline-formula> <tex-math notation="LaTeX">Q </tex-math></inline-formula> network with dueling architecture (DDDQN) is proposed to obtain the optimal payment strategies of platforms. To evaluate the performance of our proposed mechanism, extensive simulations are conducted to show the superiority of our proposed mechanism compared with state-of-the-art approaches.
The diurnal variation of photosynthesis, light response curve and CO
response curve in Epimedium brevicornu Maxim leaves were determined with Li-6400 photosynthesis system to evaluate the ...photosynthesis of E. brevicornu. Fluorescence of chlorophyll in the leaves were determined with PAM-2500 portable chlorophyll fluorescence apparatus in the study. The results showed that the midday depression of photosynthesis was very obvious in the E. brevicornu leaves. The light compensation point of E. brevicornu leaves was about 15 µmol m
s
. The light saturation point of E. brevicornu leaves was below 800 µmol m
s
, which was lower than the general sunlight intensity at noon in summer. The CO
saturation point of E. brevicornu leaves was much higher than the content of CO
in general air. E. brevicornu was a typical shade plant and could survive in very low sunlight. E. brevicornu could not endure strong sunlight and high air temperature. The net photosynthetic rate of E. brevicornu leaves linearly correlated with the content of CO
in the leaf chamber when the content was below CO
saturation point. E. brevicornu possessed great potential of photosynthesis.
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