Publications by authors named "Yahui Tian"

15 Publications

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Numerical Analysis of Viscous Dissipation in Microchannel Sensor Based on Phononic Crystal.

Micromachines (Basel) 2021 Aug 21;12(8). Epub 2021 Aug 21.

State Key Laboratory of Space Power-Source Technology, Shanghai Institute of Space Power-Sources, Shanghai 200245, China.

Phononic crystals with phononic band gaps varying in different parameters represent a promising structure for sensing. Equipping microchannel sensors with phononic crystals has also become a great area of interest in research. For building a microchannels system compatible with conventional micro-electro-mechanical system (MEMS) technology, SU-8 is an optimal choice, because it has been used in both fields for a long time. However, its mechanical properties are greatly affected by temperature, as this affects the phononic bands of the phononic crystal. With this in mind, the viscous dissipation in microchannels of flowing liquid is required for application. To solve the problem of viscous dissipation, this article proposes a simulation model that considers the heat transfer between fluid and microchannel and analyzes the frequency domain properties of phononic crystals. The results show that when the channel length reaches 1 mm, the frequency shift caused by viscous dissipation will significantly affect detecting accuracy. Furthermore, the temperature gradient also introduces some weak passbands into the band gap. This article proves that viscous dissipation does influence the band gap of phononic crystal chemical sensors and highlights the necessity of temperature compensation in calibration. This work may promote the application of microchannel chemical sensors in the future.
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http://dx.doi.org/10.3390/mi12080994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400026PMC
August 2021

A rational design of g-CN-based ternary composite for highly efficient H generation and 2,4-DCP degradation.

J Colloid Interface Sci 2021 Oct 20;599:484-496. Epub 2021 Apr 20.

Engineering Research Center for Functional Ceramics of the Ministry of Education, School of Optical and Electronic Information, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, PR China; Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, PR China. Electronic address:

In this work, g-CN based ternary composite (CeO/CN/NH-MIL-101(Fe)) has been fabricated via hydrothermal and wet-chemical methods. The composite showed superior photoactivities for HO reduction to produce H and 2,4-dichlorophenol (2,4-DCP) degradation. The amount of H evolved over the composite under visible and UV-visible irradiations is 147.4 µmol·g·h and 556.2 µmol·g·h, respectively. Further, the photocatalyst degraded 87% of 2,4-DCP in 2 hrs under visible light irradiations. The improved photoactivities are accredited to the synergistic-effects caused by the proper band alignment with close interfacial contact of the three components that significantly promoted charge transfer and separation. The 2,4-DCP degradation over the composite is dominated by OH radical rather than h and O as investigated by scavenger trapping experiments. This is further supported by the electron para-magnetic resonance (EPR) study. This work provides new directions for the development of g-CN based highly efficient ternary composite materials for clean energy generation and pollution control.
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http://dx.doi.org/10.1016/j.jcis.2021.04.049DOI Listing
October 2021

GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence.

Front Oncol 2020 12;10:824. Epub 2020 Jun 12.

Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes (TSGs) play a critical role in restricting tumorigenesis and impact the therapeutic effect of various treatments. However, TSGs remain to be systemically determined in lung cancer. Here, we identified GATA6 as a potent lung cancer TSG. GATA6 inhibited lung cancer cell growth and tumorigenesis . Mechanistically, GATA6 upregulated p53 and p21 mRNA while it inhibited AKT activation to stabilize p21 protein, thus inducing lung cancer cell senescence. Furthermore, we showed that ectopic expression of GATA6 led to dramatic slowdown of growth rate of established lung tumor xenograft .
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http://dx.doi.org/10.3389/fonc.2020.00824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304445PMC
June 2020

Blocking interaction between SHP2 and PD-1 denotes a novel opportunity for developing PD-1 inhibitors.

EMBO Mol Med 2020 06 11;12(6):e11571. Epub 2020 May 11.

MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.

Small molecular PD-1 inhibitors are lacking in current immuno-oncology clinic. PD-1/PD-L1 antibody inhibitors currently approved for clinical usage block interaction between PD-L1 and PD-1 to enhance cytotoxicity of CD8 cytotoxic T lymphocyte (CTL). Whether other steps along the PD-1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA-approved chemical for treating methemoglobinemia, potently inhibits PD-1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine-secreting activity of CTL inhibited by PD-1. Mechanistically, MB blocks interaction between Y248-phosphorylated immunoreceptor tyrosine-based switch motif (ITSM) of human PD-1 and SHP2. MB enables activated CTL to shrink PD-L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD-1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA-approved chemical capable of potently inhibiting the function of PD-1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD-1 signaling axis.
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http://dx.doi.org/10.15252/emmm.201911571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278553PMC
June 2020

Therapies after first-line afatinib in patients with m NSCLC in Japan: retrospective analysis of LUX-Lung 3.

Future Oncol 2020 Feb 10;16(4):49-60. Epub 2020 Jan 10.

Third Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.

Acquired resistance to EGFR tyrosine kinase inhibitors is inevitable in non-small-cell lung cancer. To inform subsequent treatment decisions, we retrospectively assessed therapies following afatinib in Japanese patients from LUX-Lung 3. LUX-Lung 3 was a randomized, open-label, Phase III study of afatinib versus cisplatin/pemetrexed in treatment-naive patients with mutation-positive (m) advanced lung adenocarcinoma. Among 47 Japanese patients who discontinued first-line afatinib, 91/81/62% received ≥one/two/three subsequent therapies. The most common second-line therapies were platinum-based chemotherapy (38%) and a first-generation EGFR tyrosine kinase inhibitor (17%). Median overall survival (afatinib vs cisplatin/pemetrexed) was 47.8 versus 35.0 months (not significant). First-line afatinib does not appear to diminish suitability for subsequent therapies in m non-small-cell lung cancer.
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http://dx.doi.org/10.2217/fon-2019-0659DOI Listing
February 2020

Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition.

Nat Commun 2019 04 10;10(1):1665. Epub 2019 Apr 10.

Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, 510632, Guangzhou, China.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes remain to be systemically identified for lung cancer. Through the genome-wide screening of tumor-suppressive transcription factors, we demonstrate here that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vivo. Ectopic GATA4 expression results in lung cancer cell senescence. Mechanistically, GATA4 upregulates multiple miRNAs targeting TGFB2 mRNA and causes ensuing WNT7B downregulation and eventually triggers cell senescence. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGF-β2 level and is significantly associated with poor prognosis. TGFBR1 inhibitors show synergy with existing therapeutics in treating GATA4-deficient lung cancers in genetically engineered mouse model as well as patient-derived xenograft (PDX) mouse models. Collectively, our work demonstrates that GATA4 functions as a tumor suppressor in lung cancer and targeting the TGF-β signaling provides a potential way for the treatment of GATA4-deficient lung cancer.
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http://dx.doi.org/10.1038/s41467-019-09295-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458308PMC
April 2019

In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis.

Proc Natl Acad Sci U S A 2018 04 9;115(17):E3978-E3986. Epub 2018 Apr 9.

State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China;

Lung cancer is the leading cause of cancer-related death worldwide. Inactivation of tumor suppressor genes (TSGs) promotes lung cancer malignant progression. Here, we take advantage of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated somatic gene knockout in a mouse model to identify bona fide TSGs. From individual knockout of 55 potential TSGs, we identify five genes, including , , , , and , whose knockout significantly promotes lung tumorigenesis. These candidate genes are frequently down-regulated in human lung cancer specimens and significantly associated with survival in patients with lung cancer. Through crossing the conditional knockout allele to the mouse model, we further find that deletion dramatically promotes lung cancer progression. The tumor-promotive effect of knockout in vivo is mainly mediated through an increase of the EZH2 level, which up-regulates the H3K27me3 level. Moreover, the -knockout lung tumors are preferentially sensitive to EZH2 inhibitor treatment. Collectively, our study provides a systematic screening of TSGs in vivo and identifies UTX as an important epigenetic regulator in lung tumorigenesis.
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http://dx.doi.org/10.1073/pnas.1716589115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924887PMC
April 2018

Multiple Interfacial [email protected]/P(VDF-HFP) Core-Shell-Matrix Films with Internal Barrier Layer Capacitor (IBLC) Effects and High Energy Storage Density.

ACS Appl Mater Interfaces 2017 Nov 10;9(46):40792-40800. Epub 2017 Nov 10.

Institute of Huazhong University of Science and Technology , 9 Yuexingsandao, Nanshan District, Shenzhen 518000, P. R. China.

Flexible nanocomposites composed of high dielectric constant fillers and polymer matrix have shown great potential for electrostatic capacitors and energy storage applications. To obtain the composited material with high dielectric constant and high breakdown strength, multi-interfacial composited particles, which composed of conductive cores and insulating shells and possessed the internal barrier layer capacitor (IBLC) effect, were adopted as fillers. Thus, [email protected] core-shell particles were prepared and loaded into the poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP)) polymer matrix. As the mass fraction of core-shell fillers increased from 2.5 wt % to 30 wt %, the dielectric constant of the films increased, while the loss tangent remained at a low level (<0.05 at 1 kHz). Both high electric displacement and high electric breakdown strength were achieved in the films with 10 wt % core-shell fillers loaded. The maximum energy storage density of 7.018 J/cm was measured at 2350 kV/cm, which shows significant enhancement than those of the pure P(VDF-HFP) films and analogous composited films with converse insulating-conductive core-shell fillers. A Maxwell-Wagner capacitor model was also adopted to interpret the efficiency of IBLC effects on the suppressed loss tangent and the superior breakdown strength. This work explored an effective approach to prepare dielectric nanocomposites for energy storage applications experimentally and theoretically.
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http://dx.doi.org/10.1021/acsami.7b10923DOI Listing
November 2017

Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular Docking.

Comb Chem High Throughput Screen 2016 ;19(9):691-704

College of Chemical Engineering, Sichuan University, Sichuan, Chengdu, 610065, China.

Aim And Objective: Anaplastic lymphoma kinase, an insulin receptor protein-tyrosine kinase, is a very attractive receptor protein target for anticancer therapy. This study was undertaken to identify novel structurally diverse anaplastic lymphoma kinase inhibitors.

Material And Method: Pharmacophore hypotheses modeling, virtual screening and molecular docking were used to detect potential inhibitors of anaplastic lymphoma kinase in this paper.

Results: After the generation of ten pharmacophore hypotheses, Hypo1 with the highest correlation value (0.981), lowest RMS (0.565), highest cost difference (83.850) along with four typical chemical features was regarded as the best hypothesis. Hypo1 contains a hydrogen bond acceptor, a hydrogen bong donor, a hydrophobic and a ring aromatic feature. And then, hypo1 was validated and used to screen three databases after screened by Lipinski's rule of five. 3015 hits screened by Hypo1 were submitted to molecular docking based on the crystal structure of anaplastic lymphoma kinase.

Conclusion: all the seven molecules formed hydrogen bond interaction with Met1199 as well as formed several other hydrogen bond interactions with different residues. All of them formed Van Der Waals interaction with hydrophobic pocket which made up of residues of Ala1148, Leu1256, Leu1196, Leu1198 Val1130 and Val1180. Some of them also formed van der Waals interaction in somewhere else of protein pocket.
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http://dx.doi.org/10.2174/1386207319666160801153455DOI Listing
August 2017

P Matrix Analysis of Surface Acoustic Waves in Piezoelectric Phononic Crystals.

IEEE Trans Ultrason Ferroelectr Freq Control 2016 05 18;63(5):757-763. Epub 2016 Feb 18.

Large time/memory costs have constituted a significant obstacle for accurately analyzing surface acoustic waves (SAWs) in large size two-dimensional (2-D) piezoelectric phononic crystals (PnCs). To overcome this obstacle, this study introduces the unit P matrix and its associated cascading. To obtain an accurate unit P matrix, the Y parameters of the SAW delay lines were derived using a three-dimensional (3-D) finite element model (FEM) with and without 2-D piezoelectric PnCs, respectively, on the transmitting path. A time window function was adopted to extract the desired signals from the P matrix analysis. Then, unit P matrix cascading was used to obtain SAW propagation parameters for the large size piezoelectric PnCs. Using this method, the SAW in aluminum (Al) /128º-YXLiNbO3 PnCs was analyzed over 150 periods. Experiments were also conducted. To choose the appropriate size of the unit P matrix, the variance between experimental results and theoretical results, and time/memory cost were compared for different periods. The results indicate that cascading by unit P matrix of 25 PnCs periods can be appropriately adopted to accurately derive the SAW propagation parameters over 150 periods. This indicates the accuracy of the unit P matrix derived by 3-D FEM and the effectiveness of P matrix analysis.
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http://dx.doi.org/10.1109/TUFFC.2016.2531079DOI Listing
May 2016

Pharmacophore-Based 3D-QSAR Modeling, Virtual Screening and Molecular Docking Analysis for the Detection of MERTK Inhibitors with Novel Scaffold.

Comb Chem High Throughput Screen 2016 ;19(1):73-96

College of Chemical Engineering, Sichuan University, Sichuan, Chengdu 610065, China.

MERTK plays an important role in cell biology and is correlated with many cancers, such as mantle cell lymphomas, pituitary adenomas, and T-cell acute lympholoblastic leukemia. So identification of new MERTK inhibitors is of extreme importance. In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR model, which had high value of coefficient of determination (R(2)=0.9061) and high value of coefficient of determination (Q(2)=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits were obtained. Subsequently, docking procedure was applied on these hits, and 840 compounds were obtained through high-throughput virtual screening (HTVS). Standard precision (SP), extra precision (XP) and rule of five were also used in virtual screening protocol. Finally, six candidates were identified as potential MERTK inhibitors, with the docking mode in MERTK analyzed.
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http://dx.doi.org/10.2174/1386207319666151203002228DOI Listing
August 2016

Ubiquitination and regulation of Smad7 in the TGF-β1/Smad signaling of aristolochic acid nephropathy.

Toxicol Mech Methods 2015 25;25(8):645-52. Epub 2015 Jun 25.

a Laboratory of Veterinary Pharmacology , Animal Science and Technology College, Beijing University of Agriculture , Beijing , China .

Aristolochic acid I (AAI) affects TGF-β1/Smad signaling, which causes AA nephropathy (AAN), but the mechanisms are not fully understood. We aimed to clarify whether Arkadia and UCH37 participate in TGF-β1/Smad signaling via Smad7, and the regulatory mechanisms of Smad7. One side, mice and cultured mouse renal tubular epithelial cells (RTECs) were treated with various AAI doses and concentrations, respectively; on the other side, RTECs were transfected with small interfering RNA (siRNA) expression vectors against Arkadia and UCH37 and then treated with 10 µg/ml AAI. And then detect the mRNA and protein levels of Smad7, UCH37, Arkadia and any other relative factors by RT-PCR and Western blotting. In kidney tissues and RTECs, the mRNA and protein levels of Smad7 decreased with increasing AAI doses concentrations by real-time PCR and Western blotting, whereas those of Arkadia, UCH37, Smad2, Smad3 and TβRI increased. Cells transfected with the Arkadia siRNA expression vector showed reduced mRNA and protein levels of vimentin, α-SMA, Smad2, Smad3 and TβRI after AAI treatment, while those of CK18 and Smad7 increased compared with those of untransfected RTECs. Conversely, cells transfected with the UCH37 siRNA expression vector showed the opposite effect on analyzed signaling molecules after AAI treatment. Arkadia and UCH37 participate in TGF-β1/Smad signaling-mediated renal fibrosis, and Smad7 blocks TGF-β1 signaling by inhibiting Smad2/Smad3 phosphorylation and enhancing the degradation of TβRI.
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http://dx.doi.org/10.3109/15376516.2015.1061082DOI Listing
August 2016

Discovery of novel NAMPT inhibitors based on pharmacophore modeling and virtual screening techniques.

Comb Chem High Throughput Screen 2014 ;17(10):868-78

College of Chemical Engineering, Sichuan University, Sichuan, Chengdu, 610065, China.

Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme taking part in main NAD biosynthetic pathway, is an attractive target for anticancer therapy. The purpose of our study is to find novel NAMPT inhibitors based on in silico drug discovery means including the generation of 3D-QSAR models, and virtual screening techniques. Firstly, ten pharmacophore models were generated by Catalyst/HypoGen algorithm. Hypo1 with high correl value (0.96), large cost (77.77), and low root mean square deviation (0.81), featured by four chemical features was selected as the best one. Subsequently, Hypo1 was validated through test set prediction and Fischer's randomization methodologies. Then we screened some public compound libraries (Asinex, Ibscreen and Natural products database) using Hypo1 for a 3D query. The screened hits were further refined by Lipinski's rule of five, ADMET properties as well as molecular docking studies. Finally, six molecules with diverse scaffolds exhibited the right pharmacophore features and good binding modes between the receptor and ligands, and were selected as possible candidates against NAMPT for further study.
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http://dx.doi.org/10.2174/1386207317666141121124139DOI Listing
September 2015

Expression of histone deacetylase-1 and p300 in aristolochic acid nephropathy models.

Toxicol Mech Methods 2014 Sep 27;24(6):377-84. Epub 2014 Jun 27.

Laboratory of Pharmacology of Chinese Veterinary Medicine, Department of Animal Science and Technology, College of Animal Science and Technology, Beijing University of Agriculture , Beijing , China.

Aristolochic acid nephropathy (AAN) is mainly caused by aristolochic acid I (AAI), but the actual mechanism is still uncertain. The current study explored the correlation among the expression of Smad7, p300, histone deacetylase-1 (HDAC1) and the development of AAN using transmission electron microscopy (TEM), RT-PCR, and western blotting in the AAN mouse model and in the AAN cell model. TEM revealed that the renal tubular epithelial cells from the AAI-treated mice presented organelle damages and nuclear deformation. We found that a certain dose of AAI caused renal fibrosis and induced renal tubular epithelial cells to differentiate into myofibroblasts. There was a gradual increase in the expression of HDAC1 mRNA and protein observed using RT-PCR and western blotting in the AAN cell model compared with the control group. Gradual decrease in the expression of Smad7 and p300 mRNA and protein was revealed in the AAN mouse and cell models compared with the control group. These results suggest that AAI dose dependently contributed to the development of AAN, and HDAC1 and p300 participate in the modulation of TGF-β/Smad pathway-mediated renal interstitial fibrosis.
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http://dx.doi.org/10.3109/15376516.2014.920448DOI Listing
September 2014
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