The competitive endogenous RNA (ceRNA) hypothesis suggests an intrinsic mechanism to regulate biological processes. However, whether the dynamic changes of ceRNAs can modulate miRNA activities ...remains controversial. Here, we examine the dynamics of ceRNAs during TGF-β-induced epithelial-to-mesenchymal transition (EMT). We observe that TGFBI, a transcript highly induced during EMT in A549 cells, acts as the ceRNA for miR-21 to modulate EMT. We further identify FN1 as the ceRNA for miR-200c in the canonical SNAIL-ZEB-miR200 circuit in MCF10A cells. Experimental assays and computational simulations demonstrate that the dynamically induced ceRNAs are directly coupled with the canonical double negative feedback loops and are critical to the induction of EMT. These results help to establish the relevance of ceRNA in cancer EMT and suggest that ceRNA is an intrinsic component of the EMT regulatory circuit and may represent a potential target to disrupt EMT during tumorigenesis.
Epithelial-to-mesenchymal transition (EMT) is a complex multistep process in which phenotype switches are mediated by a network of transcription factors (TFs). Systematic characterization of all ...dynamic TFs controlling EMT state transitions, especially for the intermediate partial-EMT state, represents a highly relevant yet largely unexplored task. Here, we performed a computational analysis that integrated time-course EMT transcriptomic data with public cistromic data and identified three synergistic master TFs (ETS2, HNF4A and JUNB) that regulate the transition through the partial-EMT state. Overexpression of these regulators predicted a poor clinical outcome, and their elimination readily abolished TGF-β-induced EMT. Importantly, these factors utilized a clique motif, physically interact and their cumulative binding generally characterized EMT-associated genes. Furthermore, analyses of H3K27ac ChIP-seq data revealed that ETS2, HNF4A and JUNB are associated with super-enhancers and the administration of BRD4 inhibitor readily abolished TGF-β-induced EMT. These findings have implications for systematic discovery of master EMT regulators and super-enhancers as novel targets for controlling metastasis.
Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may ...provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis.
Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and ...algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2–3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor Nature 574, 505 (2019). We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.
Currently, organic electrode materials have shown promising prospects in lithium-ion batteries (LIBs). However, the practical application of organic electrode materials is severely hindered by the ...intrinsic low electrical conductivity and poor cycle stability. Herein, we present a novel polyimide (NBI-PI) which contains extended π-conjugated naphthalene ring and Schiff-base structure as an anode material. The NBI-PI has abundant active sites and crystallized nature. The organic anode based on NBI-PI for LIBs exhibit good reversible capacity of 627.8 mA h g−1 at 0.25 A g−1 after 200 cycles, and display reasonable rate performance of 217 mA h g−1 at 2 A g−1. When the batteries are cycled at 2 A g−1, capacity retention of 85.7% is attained after 1600 electrochemical cycles. This work demonstrates a facile and practical strategy to develop high-performance organic anode materials for lithium-ion batteries.
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•Employing a novel polyimide Schiff base as organic lithium-ion batteries.•Extended π-conjugated structure and abundant redox active sites are achieved.•High comprehensive electrochemical performance is realized.•The influence of electronic structure on redox activity is discussed.
•Asphalt prevents the phase change process of polyethylene glycol.•Polyethylene glycol has a complicated effect on the rheological property of asphalt.•The asphalt mixture containing polyethylene ...glycol is cooled by a maximum of 3.3 °C.•Polyethylene glycol has an adverse effect on the shear strength of asphalt mixture.
Polyethylene glycol (PEG) has been used as a phase change material in asphalt mixture to cool asphalt pavement in summer. However, the PEG is much likely to leak and then influence its performance. This study aimed at studying the interaction between PEG and asphalt for phase change effect. Laboratory tests were conducted to evaluate the influence of PCM on asphalt/asphalt mixture performance, including microscopic test, dynamic shear rheometer test, indoor irradiation test and shear strength test. The results showed that the measured phase change enthalpy of PEG/asphalt composite was lower than theoretical results. Based on the observed FTIR spectra and fluorescence images, the PEG was found evenly distributed in the asphalt at a low content. The results of frequency and temperature sweep tests indicated that the liquid state of PEG could improve the elastic property of PAC. Furthermore, the zero shear viscosity at 40–60 °C and the non-recoverable compliance at 3.2 kPa and 12.8 kPa both increased due to the addition of PEG. The peak temperature of the PEG/asphalt mixture with 20% PEG was 3.3 °C lower than control asphalt mixture. However, the shear strength of PEG/asphalt mixture decreased by 20.3%, compared with control asphalt mixture. The study findings indicate that it is desired to propose an effective method to incorporate phase change material in asphalt mixture in order to reduce the influences of PCM leakage on performance.
•BnWRKY41-1 has a similar function in anthocyanin biosynthesis with AtWRKY41 in Arabidopsis thaliana rosette leaves.•The wrky41 mutation caused a substantial increase in the amount of anthocyanins in ...A. thaliana rosette leaves.•Several key genes involved in anthocyanin biosynthesis were significantly up-regulated in wrky41-2 rosette leaves.•Overexpression of BnWRKY41-1 restored the higher anthocyanin content of wrky41-2 rosette leaves in A. thaliana.•Overexpression of BnWRKY41-1 prevented elevated expression of genes for anthocyanin biosynthesis in wrky41-2 rosette leaves.
Previous studies have shown that a plant WRKY transcription factor, WRKY41, has multiple functions, and regulates seed dormancy, hormone signaling pathways, and both biotic and abiotic stress responses. However, it is not known about the roles of AtWRKY41 from the model plant, Arabidopsis thaliana, and its ortholog, BnWRKY41, from the closely related and important oil-producing crop, Brassica napus, in the regulation of anthocyanin biosynthesis. Here, we found that the wrky41 mutation in A. thaliana resulted in a significant increase in anthocyanin levels in rosette leaves, indicating that AtWRKY41 acts as repressor of anthocyanin biosynthesis. RNA sequencing and quantitative real-time PCR analysis revealed increased expression of three regulatory genes AtMYB75, AtMYB111, and AtMYBD, and two structural genes, AT1G68440 and AtGSTF12, all of which contribute to anthocyanin biosynthesis, in the sixth rosette leaves of wrky41-2 plants at 20 days after germination. We cloned the full length complementary DNA of BnWRKY41-1 from the C2 subgenome of the B. napus genotype Westar and observed that, when overexpressed in tobacco leaves as a fusion protein with green fluorescent protein, BnWRKY41-1 is localized to the nucleus. We further showed that overexpression of BnWRKY41-1 in the A. thaliana wrky41-2 mutant rescued the higher anthocyanin content phenotype in rosette leaves of the mutant. Moreover, the elevated expression levels in wrky41-2 rosette leaves of several important regulatory and structural genes regulating anthocyanin biosynthesis were not observed in the BnWRKY41-1 overexpressing lines. These results reveal that BnWRKY41-1 has a similar role with AtWRKY41 in regulating anthocyanin biosynthesis when overexpressed in A. thaliana. This gene represents a promising target for genetically manipulating B. napus to increase the amounts of anthocyanins in rosette leaves.
•The effect of ECC construction method on shear properties of ECC-to-concrete interface was studied.•The construction method of spraying ECC had an obvious decreasing effect on interface tensile ...strength.•A shear strength mechanical model and a shear stress-slip model of ECC-to-concrete interface were proposed.
This paper reveals an investigation of the influences of ECC mixture construction method (i.e., common casting and spraying ECC), ECC strength grade, interface roughness of concrete substrate, and polyvinyl alcohol (PVA) fiber type on shear properties of ECC-to-concrete interface. The test results show that two failure modes of interface shear failure and ECC failure were observed. The roughness degree of concrete substrate had a strong effect on the failure mode, while ECC strength grade, ECC mixture construction method, and PVA fiber type had almost no influence on the failure mode. The shear load-slip curves of all specimens were basically similar. Compared to the casting ECC, the spraying ECC had an obvious decreasing effect on interface shear strength. The ECC strength grade and roughness degree of concrete substrate had a significant influence on interface shear strength, and higher ECC compressive strength and coarser interface could cause higher interface shear strength. On the contrary, PVA fiber type had a slight influence on interface shear strength. Based on the micro-bonding mechanism and test results of shear load-slip curves, a shear strength mechanical model and a shear stress-slip model of ECC-to-concrete interface were proposed to predict interface shear strength and shear stress-slip curve, respectively.
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To ensure a long-term quantum computational advantage, the quantum hardware should be upgraded to withstand the competition of continuously improved classical algorithms and ...hardwares. Here, we demonstrate a superconducting quantum computing systems Zuchongzhi 2.1, which has 66 qubits in a two-dimensional array in a tunable coupler architecture. The readout fidelity of Zuchongzhi 2.1 is considerably improved to an average of 97.74%. The more powerful quantum processor enables us to achieve larger-scale random quantum circuit sampling, with a system scale of up to 60 qubits and 24 cycles, and fidelity of FXEB=(3.66±0.345)×10-4. The achieved sampling task is about 6 orders of magnitude more difficult than that of Sycamore Nature 574, 505 (2019) in the classic simulation, and 3 orders of magnitude more difficult than the sampling task on Zuchongzhi 2.0 arXiv:2106.14734 (2021). The time consumption of classically simulating random circuit sampling experiment using state-of-the-art classical algorithm and supercomputer is extended to tens of thousands of years (about 4.8×104 years), while Zuchongzhi 2.1 only takes about 4.2 h, thereby significantly enhancing the quantum computational advantage.
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