In this work, we demonstrate two types of heterogeneous irradiated-pristine polyethylene nanofiber junctions, 'heavily-irradiated-pristine' (HI-P) and 'lightly-irradiated-pristine' (LI-P) junctions, ...as high-performance solid-state thermal diodes. The HI-P junction rectifies heat flux in a single direction, while the LI-P junction shows dual-directional rectification under different working temperatures. We accurately model the phase transition of polyethylene nanofibers with a finite temperature range rather than a step function. The finite-temperature-range model suggests that the rectification factor increases with temperature bias and there is a minimum threshold of temperature bias for notable rectification. Besides, the finite-temperature-range model shows better prediction for the heat flow data from experiments, while the step function model tends to overestimate the rectification performance around the optimal length fraction of irradiation. Although both the models show that an optimal rectification occurs when the interface temperatures in the forward and the reverse biases are equal, the optimized rectification factor is determined by the temperature bias and the temperature range of phase transition. This work elucidates the influence of both the temperature bias and the temperature range of phase transition on thermal rectification performance, which could incredibly benefit the evaluation and design of thermal diodes.
The error measurement of fiscal accounting data can effectively slow down the change of financial assets. Based on deep neural network theory, we constructed an error measurement model for fiscal and ...tax accounting data, and we analyzed the relevant theories of fiscal and tax performance evaluation. By establishing a batch evaluation index of finance and tax accounting, the model can monitor the changing trend of the error of urban finance and tax benchmark data scientifically and accurately, as well as solve the problem of high cost and delay in predicting the error of finance and tax benchmark data. In the simulation process, based on the panel data of credit unions, the entropy method and a deep neural network were used to measure the fiscal and tax performance of regional credit unions. In the example application, the model, combined with MATLAB programming, calculated the contribution rate of regional higher fiscal and tax accounting input to economic growth. The data show that the contribution rates of some fiscal and tax accounting input, commodity and service expenditure, other capital expenditure and capital construction expenditure to regional economic growth are 0.0060, 0.0924, 0.1696 and -0.0822, respectively. The results show that the proposed method can effectively map the relationships between variables.
Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene ...receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), and found that SEL201-treated KIT-mutant melanoma cells had lower oncogenicity and reduced metastatic ability. Clinically, tumors from melanoma patients harboring KIT mutations displayed a marked increase in MNK1 and phospho-eIF4E. Thus, our studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and support blocking MNK1/2 as a potential strategy to treat patients positive for KIT mutations.
Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and ...eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2β mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2β and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation.
G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 motifs in mRNAs, ...especially in their coding sequences. Herein, we show that Aven stimulates the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase associated with the Aven complex and was required for optimal translation of G4 mRNAs. Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins resulting in reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells.
Microinvasive breast cancer (MBC for short) is a rare entity with the decision of axillary surgery under debate in clinical practice. We aimed to unravel the lymph node metastasis (LNM) rate, ...axillary surgery, and prognosis of MBC based on 11,692 patients derived from the Surveillance Epidemiology and End Results (SEER) database between 2003 and 2015. In this retrospective study, 19.5% (2276/11,692) of patients received axillary lymph node dissection (ALND), 80.5% (9416/11,692) received non-ALND. In the total cohort, 10-year breast cancer-specific survival (BCSS) was 96.3%, and the LNM rate was 6.4% (754/11,692). Multivariate analyses showed that LNM had the strongest predictive weight (N3, HR 14.200, 95% CI 7.933−25.417; N2, HR 12.945, 95% CI 7.725−21.694; N1, HR 3.05, 95% CI 2.246−4.140, all p < 0.001). Kaplan−Meier analyses showed that ALND did not confer a survival benefit on 10-year BCS in patients with N0 (94.7% vs. 97.1%, p < 0.001) and in patients with 1−2 positive nodes (92.1% vs. 89.5%, p = 0.355), respectively, when compared to non-ALND. Our study demonstrated that the vast majority of MBC have a low LNM rate and excellent prognosis; patients with LNM showed poor prognosis. Assessment of lymph node status is necessary, and non-ALND surgery is required and sufficient for MBC with 0−2 positive nodes.
Flexible manipulations of morphology and composition have been considered as an art to achieve excellent microwave absorption performance for absorbers derived from metal-organic frameworks (MOFs). ...In this work, a strategy combining ligand-exchange induced hollow engineering and high-temperature one-step sulfuration has been proposed to fabricate the Co9S8/Co@N, S dual-doped carbon-based absorbers with tailored solid, yolk-shelled and entirely hollow polyhedral morphologies. The progressive hollow engineering not only enables composition control in the sulfuration process, but also endows the proposed absorbers with superior microwave absorption capacity due to the enhanced conductivity loss and Maxwell-Wagner polarization as well as optimized impedance matching. The yolk-shelled Co9S8/Co@N, S dual-doped carbon-based composite achieves a broad effective absorption bandwidth of 5.13 GHz at 1.88 mm with 20 wt% loading and realizes a minimum microwave loss of − 51.78 dB @ 11.63 GHz with 2.37 mm. This work reveals that the joint strategy of ligand-exchange induced hollow engineering and gas-solid reactive thermal process is an effective path to construct high-efficient lightweight multi-interfacial microwave absorbers for addressing the electromagnetic pollutions.
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•Ligand-exchange etching facilitates tailored cavity structure in MOF-derived MAMs.•Progressive hollow engineering enables composition control in sulfuration process.•Proposed yolk-shelled absorber achieves an EAB of 5.13 GHz with 20 wt% filling.•Synergy of attenuation and impedance matching realizes superior EM absorption.
Double‐network hydrogels have outstanding mechanical characteristics but mostly suffer from poor self‐healing performance since most hydrogels are chemically crosslinked via covalent links for each ...network. In this work, a tough and self‐healing double network hydrogel with multiple dynamic non‐covalent bonds is developed by combining the hydrophobically modified polyacrylamide (HPAM) with a thermally reversible potassium ion crosslinked κ‐carrageenan (K+C) network through a dual physical crosslinked network strategy. Being the multiple dynamic non‐covalent bond interactions and dual physical crosslink networks, the K+C/HPAM DN hydrogel exhibits excellent mechanical characteristics (tensile strength: 1.86 MPa, tensile strain: 1637%) and good self‐healing ability (maximum stress self‐healing efficiency: 87%, maximum tensile strength after self‐healing: 0.95 MPa). Due to the three‐dimensional pore structure and the conductive ions in the system, the K+C/HPAM DN hydrogel also achieves good strain sensing capabilities with a strain sensitivity of 2.98 (gauge factor, GF) in the 100% strain range. Even after being cut and self‐healed, the gel still exhibits good strain sensing capabilities (GF = 2.79), which is still better than the most similar DN hydrogel strain sensors in sensitivity. We believe this work offers a new material for self‐healing flexible strain sensors.
The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine ...motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5' TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5' TOP motif but that 5' UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5' UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5' UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5' UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5' UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5' UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells.
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