An Engineered Outer Membrane-Defective Escherichia coli Secreting Protective Antigens against Streptococcus suis via the Twin-Arginine Translocation Pathway as a Vaccine

( Wenyu Li ),( Fan Yin ),( Zixuan Bu ),( Yuying Liu ),( Yongqing Zhang ),( Xiabing Chen ),( Shaowen Li ),( Lu Li ),( Rui Zhou ),( Qi Huang ) 한국미생물 · 생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.3

Live bacterial vector vaccines are one of the most promising vaccine types and have the advantages of low cost, flexibility, and good safety. Meanwhile, protein secretion systems have been reported as useful tools to facilitate the release of heterologous antigen proteins from bacterial vectors. The twin-arginine translocation (Tat) system is an important protein export system that transports fully folded proteins in a signal peptide-dependent manner. In this study, we constructed a live vector vaccine using an engineered commensal Escherichia coli strain in which amiA and amiC genes were deleted, resulting in a leaky outer membrane that allows the release of periplasmic proteins to the extracellular environment. The protective antigen proteins SLY, enolase, and Sbp against Streptococcus suis were targeted to the Tat pathway by fusing a Tat signal peptide. Our results showed that by exploiting the Tat pathway and the outer membrane-defective E. coli strain, the antigen proteins were successfully secreted. The strains secreting the antigen proteins were used to vaccinate mice. After S. suis challenge, the vaccinated group showed significantly higher survival and milder clinical symptoms compared with the vector group. Further analysis showed that the mice in the vaccinated group had lower burdens of bacteria load and slighter pathological changes. Our study reports a novel live bacterial vector vaccine that uses the Tat system and provides a new alternative for developing S. suis vaccine.

FEZF2 inhibits the growth of triple-negative breast cancer cells through EZH2/PD-L1 and enhances anti-tumor immunity in vivo

Li Wenyu,Liu Hu,Li Wenjuan,Zhang Qiujun,Zhang Qianyu,Hu Dandan 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.3

Background Triple-negative breast cancer (TNBC) is characterized by high aggressiveness, heterogeneity, and poor prognosis. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, a crucial type of immune checkpoint inhibitor therapy, have been proven to be a promising strategy for the TNBC treatment. Forebrain embryonic zinc finger 2 (FEZF2) is dysregulated in various cancers and participates in the tumor progression. However, its role and mechanism in TNBC remain unknown. Objectives To investigate whether FEZF2 is involved in the progression of TNBC via EZH2/PD-L1 axis. Results The expression of FEZF2 was downregulated in TNBC. Overexpression of FEZF2 reduced cell viability and enhanced cell apoptosis in both MDA-MB-231 and BT-549 cells. Meanwhile, upregulation of FEZF2 decreased the relative protein expression of EZH2 and PD-L1, which was restored by overexpression of EZH2 in both cells. Moreover, overexpression of PD-L1 neutralized the inhibitory effect of the FEZF2 overexpression on the cell viability in MDA-MB-231 and BT-549 cells. Furthermore, overexpression of FEZF2 reduced the tumor weight and volume, and increased numbers of CD8+ tumor-infiltrating lymphocytes in xenografted mice. Conclusion Overexpression of FEZF2 inhibited the proliferation and enhanced the apoptosis of TNBC cells through EZH2/PD-L1 axis, as well as promoted anti-tumor immunity in vivo. Background Triple-negative breast cancer (TNBC) is characterized by high aggressiveness, heterogeneity, and poor prognosis. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, a crucial type of immune checkpoint inhibitor therapy, have been proven to be a promising strategy for the TNBC treatment. Forebrain embryonic zinc finger 2 (FEZF2) is dysregulated in various cancers and participates in the tumor progression. However, its role and mechanism in TNBC remain unknown. Objectives To investigate whether FEZF2 is involved in the progression of TNBC via EZH2/PD-L1 axis. Results The expression of FEZF2 was downregulated in TNBC. Overexpression of FEZF2 reduced cell viability and enhanced cell apoptosis in both MDA-MB-231 and BT-549 cells. Meanwhile, upregulation of FEZF2 decreased the relative protein expression of EZH2 and PD-L1, which was restored by overexpression of EZH2 in both cells. Moreover, overexpression of PD-L1 neutralized the inhibitory effect of the FEZF2 overexpression on the cell viability in MDA-MB-231 and BT-549 cells. Furthermore, overexpression of FEZF2 reduced the tumor weight and volume, and increased numbers of CD8+ tumor-infiltrating lymphocytes in xenografted mice. Conclusion Overexpression of FEZF2 inhibited the proliferation and enhanced the apoptosis of TNBC cells through EZH2/PD-L1 axis, as well as promoted anti-tumor immunity in vivo.

Relationship between Future Time Orientation, Career Adaptability Focusing on the Mediating Role of Procrastination

Wenyu Li,이수진 사단법인 한국융합기술연구학회 2023 아시아태평양융합연구교류논문지 Vol.9 No.5

Recently China has enacted many strict measures due to the COVID-19 pandemic. As college students spend most of their time taking online classes, procrastinating due to the lack of management has become a common thing. All these have intensified the confusion and anxiety among college students as they think about their future career. To explore the relationship between future time orientation and career adaptability and the mediating role of procrastination, this study took 1029 Chinese college students as research targets through online questionnaires which adopt the Future-orientation Questionnaire, the Career Adaptability Questionnaire and the Short General Procrastination Scale in 2022. Data were analyzed by SPSS 26.0 and Mplus 8.0, include descriptive statistics, t test and other methods. The results showed that (1) there were significant differences in future time orientation, career adaptability and procrastination considering demographic variables (sex, only child, studying abroad, and education). (2) There was a significant positive correlation between future time orientation and career adaptability. There was a significant negative correlation between procrastination and future time orientation and career adaptability. (3) Procrastination acted as a partial mediator in the relationship between future time orientation and career adaptability. The results can provide new ideas for how to improve the adaptability of college students.

A Comparative Study on the Insulation Ageing of 10 kV XLPE Cable via Accelerated Electrical Test and Accelerated Water Tree Test

Li Weiwei,Zheng Wenyue,Ren Lulu,Li Huan,Zhao Xuetong,Wang Can,Li Jianying 대한전기학회 2022 Journal of Electrical Engineering & Technology Vol.17 No.1

Medium and high voltage XLPE cables were widely used in urban distribution network. The electric-thermal eff ect of the cable conductor and water in the running environment are two important factors that cause ageing of cable insulating material. In this work, accelerated electrical test (AET) and accelerated water tree test (AWTT) on 10 kV XLPE cable were carried out for 1440 h, 2880 h and 4320 h, respectively. The physicochemical and dielectric properties of both aged and unaged XLPE samples were tested. Physicochemical investigation of Fourier Transform Infrared (FTIR) spectroscopy and X-Ray Diff raction (XRD) show that higher carbonyl groups index, and lower crystallinity of the XLPE insulating materials were generated in AWTT process than that in AET process. The thermal decomposition process of the AWTT XLPE are complicated, presenting a multi-peak phenomenon in the diff erential thermogravimetry (DTG) curve. The insulating strength of the samples after AWTT is monotonically decreased from 23.03 kV to 21.74 kV with ageing time. The dielectric properties show that the permittivity and dielectric loss of AWTT samples increased more severely than that of AET samples, with a new dielectric relaxation peak appearing at around 100 Hz. The combination of physicochemical and dielectric results reveals that AWTT process leads to more serious degradation for XLPE insulating materials. A schematic illustration is given to elucidate the development of micro defects in XLPE during the AET and AWTT processes.

Circular RNA expression profile of systemic lupus erythematosus and its clinical significance as a potential novel biomarker

Li Wenyu,Fan Runge,Zhou Cheng,Wei Yue,Lin Shunsheng,Wen Sijian,Zeng Wen,Hou Wei,Zhao Cheng,Lin Youkun 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear. Objective: We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE. Method: RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis. Results: The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P < 0.05), and hsa_circ_0006689 expression in PBMCs correlated with the SLEDAI score (P < 0.05). Furthermore, addition of hsa_circ_0006689 expression increased the sensitivities of anti-dsDNA antibody and anti-Sm antibody levels for SLE diagnosis (from 29.03 to 61.30% and 32.26-71.00%, respectively). Conclusion: Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis.

Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

Xueying Li,He Huang,Bing Xu,Hongqiang Guo,Yingcheng Lin,Sheng Ye,Jiqun Yi,Wenyu Li,Xiangyuan Wu,Wei Wang,Hongyu Zhang,Derong Xie,Jiewen Peng,Yabing Cao,Xingxiang Pu,Chengcheng Guo,Huangming Hong,Zhao 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3

Purpose Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. Materials and Methods Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. Results Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ! 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. Conclusion R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ! 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis

Su Wei,Guo Yingying,Wang Qianqian,Ma Lu,Zhang Qing,Zhang Yuhan,Geng Yiding,Jin Tongzhu,Guo Jiayu,Yang Ruoxuan,Niu Zhihui,Ren Lingxue,Wang Yanjie,Ning Zhiwei,Li Wenyue,He Wenxin,Sun Jian,Li Tianyu,Li Z 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

Removal of ammonia nitrogen from wastewater by three-dimensional electrode system based on solid waste containing iron

Wenyu Yang,Demin Li,Jing Zhang,Zhaoyang Wang 대한환경공학회 2022 Environmental Engineering Research Vol.27 No.6

In order to solve the problem of ammonia nitrogen pollution, three-dimensional electrode electrochemical oxidation technology is utilized to transform ammonia nitrogen. The influence of influent pH, power supply and electrolyte concentration on ammonia nitrogen removal by three-dimensional electrode method and its mechanism were discussed by single factor variable analysis. The particle electrode by emission scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). The results show that the removal efficiency of ammonia nitrogen by three-dimensional electrode is higher than that by two-dimensional electrode. When the aqueous solution is neutral, the direct and indirect oxidation reactions of ammonia nitrogen can reach the best state, and the removal efficiency is the highest. Within a certain range, the electrolytic efficiency will increase with the increase of electrolytic voltage and electrolyte concentration. The reduction of electrode spacing in a certain range can enhance the direct oxidation of ammonia nitrogen and improve the electrolysis efficiency of ammonia nitrogen. Under the conditions of pH 7, power supply voltage 14 V, electrolyte concentration 0.1 mol/L, electrode spacing 1 cm, electrolytic time 50 min, ammonia nitrogen can be completely removed from the three-dimensional electrode

MAPK4 silencing in gastric cancer drives liver metastasis by positive feedback between cancer cells and macrophages

Li Shuang,Guo Dongyang,Sun Qiang,Zhang Lu,Cui Yun,Liu Min,Ma Xixi,Liu Yiman,Cui Wenyu,Sun Leimin,Teng Lisong,Wang Liangjing,Lin Aifu,Liu Wei,Zhuo Wei,Zhou Tianhua 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Liver metastasis is a major cause of death in gastric cancer patients, but the underlying mechanisms are poorly understood. Through a combination of in vivo screening and transcriptome profiling followed by quantitative RT-PCR and tissue array analyses, we found that mitogen-activated protein kinase 4 (MAPK4) downregulation in gastric cancer tissues from patients is significantly associated with liver metastasis and poor prognosis. The knockdown of MAPK4 in gastric cancer cells promotes liver metastasis in orthotopic mouse models. MAPK4 depletion in gastric cancer cells induces the secretion of macrophage migration inhibitory factor (MIF) to polarize tumor-associated macrophages (TAMs) in orthotopic xenograft tumors. Moreover, TAMs activate epithelial–mesenchymal transition of gastric cancer cells to suppress MAPK4 expression, which further increases MIF secretion to polarize TAMs. Taken together, our results suggest a previously undescribed positive feedback loop between cancer cells and macrophages mediated by MAPK4 silencing that facilitates gastric cancer liver metastasis.

Progressive collapse of steel-framed gravity buildings under parametric fires

Jian Jiang,Wenyu Cai,Guo-Qiang Li,Wei Chen,Jihong Ye 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.36 No.4

This paper investigates the progressive collapse behavior of 3D steel-framed gravity buildings under fires with a cooling phase. The effect of fire protections and bracing systems on whether, how, and when a gravity building collapses is studied. It is found that whether a building collapses or not depends on the duration of the heating phase, and it may withstand a “short-hot” fire, but collapses under a mild fire or a “long-cool” fire. The collapse time can be conservatively determined by the time when the temperature of steel columns reaches a critical temperature of 550 °C. It is also found that the application of a higher level of fire protection may prevent the collapse of a building, but may also lead to its collapse in the cooling phase due to the delayed temperature increment in the heated members. The tensile membrane action in a heated slab can be resisted by a tensile ring around its perimeter or by tensile yielding lines extended to the edge of the frame. It is recommended for practical design that hat bracing systems should be arranged on the whole top floor, and a combination of perimeter and internal vertical bracing systems be used to mitigate the fire-induced collapse of gravity buildings. It is also suggested that beam-to-column connections should be designed to resist high tensile forces (up to yielding force) during the cooling phase of a fire.