The prognostic significance of tumor-infiltrating lymphocytes in cervical cancer

Mengdi He,Yiying Wang,Guodong Zhang,Kankan Cao,Moran Yang,Haiou Liu 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.3

Objective: To predict the prognosis of cervical cancer, we constructed a novel model with 5specific cell types and identified a potential biomarker. Methods: We employed CIBERSORT and xCell method to evaluate the abundances of 23cells types in tumor microenvironment. Five specific cell types were filtrated to determinedifferent immunotypes by applying least absolute shrinkage and selection operator (LASSO)Cox regression method. The expression of immune checkpoints (ICPs) and effectors werevalidated by immunohistochemistry. Correlation analysis was performed to examine therelevance between PIK3CA mutational status and ICPs. Results: Unsupervised clustering of patients on the basis of tumor infiltrating lymphocytesand fibroblasts identified patients with shorter overall survival (OS) (hazard ratio[HR]=3.0729; 95% confidence interval [CI]=1.5103–6.2522; p=0.0118). An immunoscore(IS) signature consisting of 5 immune cell types infiltrating in tumor core (CD8T, activatedNK cells, neutrophils, activated mast cells, macrophages) was constructed using LASSO Coxregression analysis. Receiver operating characteristic curves confirmed that the area underthe curve of IS was significantly higher to that of International Federation of Gynecology andObstetrics staging alone (0.637 vs. 0.55). Survival analysis revealed patients in high IS groupexhibited a poorer OS (HR=3.0113; 95% CI=1.8746–4.8373; p<0.0001). The multivariateanalysis indicated the IS was an independent prognostic factor. In addition, the lower ISrelated to higher expression of ICPs and neoantigen load. Conclusions: The identification of IS in cervical cancer tissues could facilitate patient riskstratification and selection of immunotherapeutic responses, but more prospective studiesare needed to assess its reliability.

Microstructure Evolution and Mechanical Properties of AA2099 Al–Li Alloy with Tailored Li‐Containing Precipitates in Uniaxial Compression at Medium Temperature

Li Hu,Mengdi Li,Weijiu Huang,Xusheng Yang,Fei Guo,Haipeng Dong 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.5

Microstructure characteristics and mechanical behavior of AA2099 Al–Li alloy with no pre-existing Li-containing precipitates(AA2099-1 sample), pre-existing δ′ precipitates (AA2099-2 sample), pre-existing T1phase (AA2099-3 sample) andpre-existing T2phase (AA2099-4 sample) are systematically investigated via isothermal uniaxial compression at 250 °C inthe present study. Experimental results demonstrate that at the onset of plastic deformation, dynamic precipitation of smallsizedT1phase occurs rapidly within AA2099-1 sample, while it will be hindered within AA2099-2 sample. The increasingplastic strain benefits to dynamic precipitation of small-sized T1phase in AA2099-2 sample. Consequently, AA2099-1 andAA2099-2 samples possess similar and intermediate mechanical behaviors. In terms of AA2099-3 sample, the existence oflarge-sized T1phase results in the maximum yielding stress. However, some regions within these large-sized T1precipitatesare suspected to be sheared by cross-slip, leading to the destruction of crystallographic structure and the formation of Almatrix intervals. This aspect is responsible for the gradual degradation in true stress-strain curve after peak stress. As forAA2099-4 sample, dynamic precipitation rarely happens during plastic deformation and the interaction between dislocationand the pre-existing T2phase belongs to Orowan looping, resulting in the minimal mechanical response. Besides,AA2099-1 sample possesses the average minimum deviation angle (MDA) of ~ 16.5° between the loading direction and the<110> crystal direction, whereas AA2099-4 sample owns the average MDA of ~ 7.5°. The difference in MDA is mainlyattributed to δ′ phase and T1phase, which will separately accelerate and postpone the rotation of orientation towards the<110> crystal direction.

Optimization of Mix Proportion of Self-compacting Concrete Based on Single Fluid Model

Xiuzhi Zhang,Chong Zhang,Mengdi Bi,Haibo Yang,Hailong Sun,Ru Mu 대한토목학회 2022 KSCE JOURNAL OF CIVIL ENGINEERING Vol.26 No.3

The study aims to optimize the mix proportion of self-compacting concrete according to the workability and compressive strength. Firstly, based on computational fluid dynamics, the flowability and filling ability of self-compacting concrete were simulated by the single-fluid model to verify the single-fluid model. And then, the simulation of casting a pre-cambered composite beam was carried out. In the end, the mix proportion was optimized considering the filling ability and the compressive strength of self-compacting concrete. The results showed that increasing sand rate can improve the workability and decrease the rheological parameters of self-compacting concrete. The mixture with a 45% sand ratio in the case of 3% silica fume alone or 43% sand ratio in the case of 30% granulated blast furnace slag and 3% silica fume had adequate filling ability and excellent long term compressive strength. Moreover, the model can be used to simulate the filling ability and passing capacity of self-compacting concrete and the maximum error between the simulation results and the actual measured value is 4.80%. When the concrete mixture is considered to be uniform, namely, without considering the effect of the aggregates, the single-fluid model can simulate the casting of self-compacting concrete.

miR-375 down-regulation of the rearranged L-myc fusion and hypoxia-induced gene domain protein 1A genes and effects on Sertoli cell proliferation

Guo, Jia,Liu, Xin,Yang, Yuwei,Liang, Mengdi,Bai, Chunyan,Zhao, Zhihui,Sun, Boxing Asian Australasian Association of Animal Productio 2018 Animal Bioscience Vol.31 No.8

Objective: This study aimed to screen and identify the target genes of miR-375 in pig Sertoli (ST) cells and to elucidate the effect of miR-375 on the proliferation of ST cells. Methods: In this study, bioinformatics software was used to predict and verify miR-375 target genes. Quantitative polymerase chain reaction (PCR) was used to detect the relationship between miR-375 and its target genes in ST cells. Enzyme-linked immunosorbent assay (ELISA) of rearranged L-myc fusion (RLF) and hypoxia-induced gene domain protein 1A (HIGD1A) was performed on porcine ST cells, which were transfected with a miR-375 mimics and inhibitor to verify the results. Dual luciferase reporter gene assays were performed to assess the interactions among miR-375, RLF, and HIGD1A. The effect of miR-375 on the proliferation of ST cells was analyzed by CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS). Results: Five possible target genes of miR-375, including RLF, HIGD1A, colorectal cancer associated 2, POU class 3 homeobox 1, and WW domain binding protein 1 like, were found. The results of quantitative PCR suggested that mRNA expression of RLF and HIGD1A had a negative correlation with miR-375, indicating that RLF and HIGD1A are likely the target genes of miR-375. The ELISA results revealed that RLF and HIGD1A were negatively correlated with the miR-375 protein level. The luminescence results for the miR-375 group cotransfected with wild-type RLF and HIGD1A vector were significantly lower than those of the miR-375 group co-transfected with the blank vector or mutant RLF and HIGD1A vectors. The present findings suggest that RLF and HIGD1A are target genes of miR-375 and that miR-375 inhibits ST cell proliferation according to MTS analysis. Conclusion: It was speculated that miR-375 affects cell proliferation through its target genes, which play an important role in the development of testicular tissue.

RNA binding protein QKI contributes to WT1 mRNA and suppresses apoptosis in ST cells

Xin Liu,Jia Guo,Mengjiao Zhou,Yuwei Yang,Mengdi Liang,Chunyan Bai,Zhihui Zhao,Boxing Sun 한국유전학회 2017 Genes & Genomics Vol.39 No.9

The RNA binding protein quaking (QKI), a key member of the STAR family, as an upstream gene could involve in much process including cell proliferation, apoptosis, differentiation and so on. However, the roles of QKI in germ cell, especially in swine testis (ST) cells, was not clear currently. And apoptosis plays important roles in the growth and development. The purpose of the present study was to clarify the relationship between QKI and apoptosis in ST cells. Firstly, our results showed that pEF1α- QKI and shQKI3 have clear effects on expression levels of QKI. Secondly, we established that QKI directly binds to WT1 3′UTR by binding with QRE-1 (2046–2052 bp, ACT AAC ) only. Furthermore, QKI overexpression significantly increased the expression levels of WT1 and Bcl-2. QKI also has the effect on delaying the degradation of WT1 mRNA. In addition, we verified that QKI had a significantly suppressed apoptosis in ST cells. Finally, pBI-WT1 could make up for shQKI3-induced decrease in WT1, Bcl-2 mRNA levels and suppress apoptosis in ST cells. The results demonstrated that QKI was an important regulatory factor that affects apoptosis by targeting WT1 gene.

Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression

Jiajia Zhang,Feize Li,Yuzhen Yin,Ning Liu,Mengqin Zhu,Han Zhang,Weihao Liu,Mengdie Yang,Shanshan Qin,Xin Fan,Yuanyou Yang,Kun Zhang,Fei Yu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: Astatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitumor immunity, which may magnify the immune responses of TAT. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy. Methods: We successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as monotherapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmunotherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzymelinked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism. Results: Such radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors. Conclusions: The tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TATCDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.