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"Liu, Qian"
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A specific tRNA half, 5'tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2
Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear.
Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5'tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5'tiRNA-His-GTG. The regulation of 5'tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments.
Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5'tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5'tiRNA-His-GTG in CRC and found that targeting 5'tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5'tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5'tiRNA-His-GTG, which renders 5'tiRNA-His-GTG to \"turn off\" hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes.
In summary, the findings revealed a specific 5'tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
Journal Article
Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood
2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C
-C
-C
scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å
), PECPS employs a one-pot formation mechanism including a \"diketide-CoA intermediate-released\" step for the formation of the C
-C
-C
scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
Journal Article
Asymmetric Evolutionary Game Analysis of Building Information Modeling (BIM) Technology Diffusion
Building Information Modeling (BIM) technology plays a pivotal role in the process of building process informatization. In the context of extensive promotion by all parties, how to effectively evaluate the promotion value of countries and enterprises is particularly important. In order to better analyze the promotion trend of the BIM technology diffusion system in China, a noncooperative evolutionary game model of BIM technology diffusion between the government and enterprises is constructed, and Vensim PLE software is used for simulation analysis in this paper. The model includes government subsidy cost and penalty, social benefit and loss, and income payment matrix of BIM technology input income and cost. The results show that enterprises need not only direct cost subsidy from the government but also indirect cost subsidy in the process of BIM technology diffusion. Appropriate government penalties can effectively promote the initiative of enterprises to adopt BIM technology; BIM has a great impact on the input income and cost of enterprises. In view of this, it is suggested that the first task for enterprises to promote the diffusion of BIM technology is to clarify the definition of BIM's high investment cost and do a good financial impact analysis.
Journal Article
EGFR-TKIs resistance via EGFR-independent signaling pathways
Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for patients harboring epidermal growth factor receptor (EGFR) mutations, especially for those with lung cancer. Unfortunately, the majority of these patients ultimately develop to the acquired resistance after a period of treatment. Two central mechanisms are involved in the resistant process: EGFR secondary mutations and bypass signaling activations. In an EGFR-dependent manner, acquired mutations, such as T790 M, interferes the interaction between TKIs and the kinase domain of EGFR. While in an EGFR-independent manner, dysregulation of other receptor tyrosine kinases (RTKs) or abnormal activation of downstream compounds both have compensatory functions against the inhibition of EGFR through triggering phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling axes. Nowadays, many clinical trials aiming to overcome and prevent TKIs resistance in various cancers are ongoing or completed. EGFR-TKIs in accompany with the targeted agents for resistance-related factors afford a promising first-line strategy to further clinical application.
Journal Article
Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors
Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.
Journal Article
Qualified to be deviant: stigma-management strategies among Chinese leftover women
This paper highlights the intersection of gender, sexuality and class in shaping the ways in which ‘leftover’ women navigate legal and social discrimination. ‘Leftover women’ is a stigmatising term in China that refers to women who do not get married by the time they reach their late twenties. Based on my fieldwork in China with queer and heterosexual ‘leftover’ women, I introduce two strategies of stigma management: ‘buying a licence to be deviant’ and ‘identity-hopping’. The former is a strategy adopted by heterosexual women with financial resources and a desire frequently expressed by queer women. ‘Buying a licence to be deviant’ refers to the strategy of accumulating sufficient financial resources to justify one's choice to be deviant and deal with the legal consequences of the evasion of the population policies. ‘Identity-hopping’ is popular among those with a lower social and financial status, who use the law's labelling function to hop from one stigmatised identity to another as a way to deal with stigma. From an intersectional lens, this paper advances law and society's study of stigma and discrimination by emphasising the hierarchy of stigmatised identities and the strategy of using the law's power of labelling identities to hop from one identity to another. It also demonstrates how the intersection of gender, sexuality and class complicates the ways in which leftover women understand and engage with the law.
Journal Article
Mechanical Performance Test and Numerical Simulation Analysis of Building Steel Plate and Concrete Composite Structure
The study aims to continuously improve the level of the construction industry, such as the improvement of construction capacity and efficiency and reduction of the project cost and construction period, and find a specific way to improve the development of the construction industry. First, the study analyzes the research status of mechanical properties of horizontal joints, vertical joints, and the overall structure of worldwide prefabricated buildings. Next, the built-in steel fabricated concrete shear wall model is established. Moreover, the quasi-static experimental analysis is conducted on the joints of the fabricated shear wall with built-in section steel. The finite element software is used to analyze the numerical simulation test of the new built-in shear wall. According to the relevant test parameters, the finite element model is constructed, and the parameters are set. Finally, the shear wall model is established and tested by a simulation experiment, and the simulation results are compared with the numerical simulation results. The final results show that the proposed connection mode of the reinforced skeleton and new fabricated joints improves the stability of prefabricated buildings. The use of the quasi-static test to test the relevant performance parameters has a short calculation time, high efficiency, and high parameter optimization accuracy. It can better simulate the actual working conditions and the actual stress-strain and damage failure conditions. Moreover, the conclusion is drawn that the shear wall structure with steel plate concrete has good ductility and deformation capacity. The study has a certain reference significance for the construction optimization of steel plate concrete prefabricated buildings and related research in the future.
Journal Article