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Influence and related mechanism of Retn gene expression on glucose uptake in 3T3-L1 cells

LI Yahui, DONG Shiyuan, YU Chao, JIANG Yu, LI Huaixing, SUN Shuhan

《医学前沿(英文)》 2007年 第1卷 第3期   页码 269-273 doi: 10.1007/s11684-007-0051-1

摘要: The aim of this article was to investigate the influence and the related mechanism of the gene on glucose uptake and insulin resistance in 3T3-L1 cells. Radioimmunoassay was used to determine glucose uptake in 3T3-L1 cells with different gene expression levels, whether cells were stimulated by insulin or not. RT-PCR and real-time RT-PCR analysis were used to determine the mRNA levels of several glucose transport proteins in 3T3-L1 cells with different gene expression levels, including insulin receptor substrate-1(IRS-1), phosphatidylinositol 3-kinase (PI-3K), AKT-2, glucose transporter-4 (GLUT-4), p38 mitogen-activated protein kinase (p38MAPK) and glycogen synthase kinase-3b (GSK-3). The glucose uptake decreased with the increase in gene expression in 3T3-L1 cells, which was independent of whether the cells were stimulated by insulin or not. The mRNA expression of two signal proteins PI-3K and AKT-2 decreased and the other two signal proteins, GSK-3 and p38MAPK, increased with overexpression in 3T3-L1 cells. Resistin could induce insulin resistance in adipocytes, which might be related to the changes of some proteins in PI-3K and Ras pathways.

关键词: 3T3-L1     influence     resistance     receptor substrate-1     transport    

Cryo-copolymerization preparation of dextran-hyaluronate based supermacroporous cryogel scaffolds for tissue engineering applications

Dongjiao ZHOU, Shaochuan SHEN, Junxian YUN, Kejian YAO, Dong-Qiang LIN

《化学科学与工程前沿(英文)》 2012年 第6卷 第3期   页码 339-347 doi: 10.1007/s11705-012-1209-1

摘要: Dextran-hyaluronate (Dex-HA) based supermacroporous cryogel scaffolds for soft tissue engineering were prepared by free radical cryo-copolymerization of aqueous solutions containing the dextran methacrylate (Dex-MA) and hyaluronate methacrylate (HA-MA) at various macromonomer concentrations under the freezing condition. It was observed that the suitable total concentration of macromonomers for the preparation of Dex-HA cryogel scaffold with satisfied properties was 5% (w/w) at the HA-MA concentration of 1% (w/v), which was then used to produce the test scaffold. The obtained cryogel scaffold with 5% (w/w) macromonomer solution had high water permeability (5.1 × 10 m ) and high porosity (92.4%). The pore diameter examined by scanning electron microscopy (SEM) was in a broad range of 50–135 μm with the mean pore diameter of 91 μm. Furthermore, the cryogel scaffold also had good elastic nature with the elastic modulus of 17.47±1.44 kPa. The culture of 3T3-L1 preadipocyte within the scaffold was investigated and observed by SEM. Cells clustered on the pore walls and grew inside the scaffold indicating the Dex-HA cryogel scaffold could be a promising porous biomaterial for applications in tissue engineering.

关键词: cryogel scaffold     tissue engineering     dextran     hyaluronate     3T3-L1 preadipocyte    

randomized trials of maintenance bacillus Calmette-Guerin instillation efficacy against recurrence of T1G3

PAN Jiangang, ZHOU Xing, CHEN Zhiguang, HAN Ruifa

《医学前沿(英文)》 2008年 第2卷 第3期   页码 259-263 doi: 10.1007/s11684-008-0049-3

摘要: Meta-analysis was used to determine whether maintenance intravesical bacillus Calmette-Guerin (BCG) could reduce recurrence after transurethral resection of tumor 1 grade 3 (T1G3) superficial bladder cancer. All available published data of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment on the treatment results in patients with superficial bladder cancer of T1G3 were selected for analysis. Both the fixed effects model and random effects model were applied, and the odds ratio () with its 95% confidence interval (CI) was used as the effect size estimate. Sensitivity analysis and publication bias determination were performed by funnel plots and comparing s of different models. Within the follow-up period, 375 of 915 (41.0%) BCG-treated patients and 332 of 733 (45.3%) non-BCG-treated patients developed tumor recurrence. In the combined results, a statistically significant difference in the s for tumor recurrence between the two treatment groups was found (randomized model combined effect 0.58, 95% CI 0.41 to 0.83, = 0.003). The stratified meta-analysis did not show any statistically significant confounding effects on the results when stratified by BCG strains. The randomized model combined effect of Pasteur F and other strains were 0.50 (95% CI 0.26 to 0.95, = 0.04) and 0.63 (95% CI 0.40 to 0.99, = 0.04), respectively. Therefore, we came to the conclusion that adjuvant maintenance instillation BCG combined with transurethral resection of bladder tumor (TURBT) is an effective conservative treatment for preventing recurrence of T1G3 bladder cancer.

CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

null

《医学前沿(英文)》 2017年 第11卷 第4期   页码 554-562 doi: 10.1007/s11684-017-0543-6

摘要:

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

关键词: CAR-T     CRISPR-Cas9     LAG-3    

mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

《医学前沿(英文)》 2021年 第15卷 第2期   页码 221-231 doi: 10.1007/s11684-020-0812-7

摘要: The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.

关键词: mTOR     cancer therapy     resistance     GSK3     protein degradation     E3 ubiquitin ligase     PD-L1    

An extended cell-based smoothed discrete shear gap method (XCS-FEM-DSG3) for free vibration analysis

NGUYEN-THOI,L. Le-ANH,V. Ho-HUU,H. Dang-TRUNG,T. NGUYEN-THOI

《结构与土木工程前沿(英文)》 2015年 第9卷 第4期   页码 341-358 doi: 10.1007/s11709-015-0302-1

摘要: A cell-based smoothed discrete shear gap method (CS-FEM-DSG3) was recently proposed and proven to be robust for free vibration analyses of Reissner-Mindlin shell. The method improves significantly the accuracy of the solution due to softening effect of the cell-based strain smoothing technique. In addition, due to using only three-node triangular elements generated automatically, the CS-FEM-DSG3 can be applied flexibly for arbitrary complicated geometric domains. However so far, the CS-FEM-DSG3 has been only developed for analyzing intact structures without possessing internal cracks. The paper hence tries to extend the CS-FEM-DSG3 for free vibration analysis of cracked Reissner-Mindlin shells by integrating the original CS-FEM-DSG3 with discontinuous and crack−tip singular enrichment functions of the extended finite element method (XFEM) to give a so-called extended cell-based smoothed discrete shear gap method (XCS-FEM-DSG3). The accuracy and reliability of the novel XCS-FEM-DSG3 for free vibration analysis of cracked Reissner-Mindlin shells are investigated through solving three numerical examples and comparing with commercial software ANSYS.

关键词: cracked Reissner-Mindlin shell     free vibration analysis     cell-based smoothed discrete shear gap method (CS-FEM-DSG3)     extended cell-based smoothed discrete shear gap method (XCS-FEM-DSG3)     smoothed finite element methods (SFEM)    

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression andhypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1

《医学前沿(英文)》 doi: 10.1007/s11684-023-1003-0

摘要: Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

关键词: Lipin3     Lipin1     hypertriglyceridemia     obesity     mitochondrial dysfunction    

Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

《医学前沿(英文)》 2022年 第16卷 第1期   页码 150-155 doi: 10.1007/s11684-021-0846-5

摘要: Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G>A, p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C>G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C>G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.

关键词: cystic fibrosis     CFTR     splicing mutation     minigene    

基于玻璃通孔的Ka波段宽带滤波封装天线 Research Article

方针1,2,张继华1,2,3,高莉彬1,2,陈宏伟1,2,李文磊1,2,梁天鹏1,2,蔡旭东1,2,蔡星周3,贾惟聪3,郭欢3,李勇3

《信息与电子工程前沿(英文)》 2023年 第24卷 第6期   页码 916-926 doi: 10.1631/FITEE.2200573

摘要: BPF单元有3对λg/4槽(缺陷微带结构)和两对λg/2 U形缝隙(缺陷地结构)。该天线实现了大带宽和高辐射效率,这可能与玻璃基板的叠加和玻璃通孔馈电有关。

关键词: 滤波封装天线;玻璃通孔;三维封装器件;激光键合    

APPLE SUMO E3 LIGASE MDSIZ1 NEGATIVELY REGULATES DROUGHT TOLERANCE

《农业科学与工程前沿(英文)》 2021年 第8卷 第2期

摘要:

Drought stress typically causes heavy losses in apple production and uncovering the mechanisms by which apple tolerates drought stress is important in apple breeding. MdSIZ1 is a SUMO (small ubiquitin-like modifier) E3 ligase that promotes SUMO binding to substrate proteins. Here, we demonstrate that MdSIZ1 in apple has a negative relationship with drought tolerance. MdSIZ1 RNAi transgenic apple trees had a higher survival rate after drought stress. During drought stress they had higher leaf water potential, reduced ion leakage, lower H2O2 and malondialdehyde contents, and higher catalase activity. In addition, MdSIZ1 RNAi transgenic plants had a higher net photosynthetic rate during the latter period of drought stress. Finally, the transgenic apple trees also altered expression levels of some microRNAs in response to drought stress. Taken together, these results indicate that apple MdSIZ1 negatively regulates drought stress by enhancing leaf water-holding capacity and antioxidant enzyme activity.

 

关键词: apple / drought tolerance / gene expression / MdSIZ1    

用以产生高纯度涡旋波束的宽带圆极化透射阵 Correspondence

邱靓婕1,2,3,4,李秀萍1,2,3,4,齐紫航1,2,3,4,赵文禹1,2,3,4,黄雨菡5

《信息与电子工程前沿(英文)》 2023年 第24卷 第6期   页码 927-934 doi: 10.1631/FITEE.2200539

摘要: 亚波长结构以及双谐振特性确保了透射单元在28.4%的1-dB透射带宽内具有稳定的相移能力。基于此,加工测试了一款由喇叭天线馈电的方形口径透射阵。得益于蜂窝状布阵方式,所设计的透射阵可在28.5 GHz到38 GHz的宽带范围中辐射l=–1且模态纯度高于0.93的涡旋波束。测试的峰值增益为22.3 dBic,3-dB轴比带宽为27.6%。

关键词: 轨道角动量;涡旋波束;透射阵;宽带;高纯度    

Self-motions of 3-RPS manipulators

Josef SCHADLBAUER, Manfred L. HUSTY, Stéphane CARO, Philippe WENGERY

《机械工程前沿(英文)》 2013年 第8卷 第1期   页码 62-69 doi: 10.1007/s11465-013-0366-3

摘要:

Recently a complete kinematic description of the 3-RPS parallel manipulator was obtained using algebraic constraint equations. It turned out that the workspace splits into two components describing two kinematically different operation modes. In this paper the algebraic description is used to give a complete analysis of all possible self-motions of this manipulator in both operation modes. Furthermore it is shown that a transition from one operation mode into the other in a self-motion is possible.

关键词: 3-RPS-manipulator     singularity     self-motion    

APPLE SUMO E3 LIGASE MDSIZ1 NEGATIVELY REGULATES DROUGHT TOLERANCE

《农业科学与工程前沿(英文)》 2021年 第8卷 第4期   页码 662-662 doi: 10.15302/J-FASE-2021408

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

《医学前沿(英文)》 2022年 第16卷 第6期   页码 883-895 doi: 10.1007/s11684-022-0919-0

摘要: Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

关键词: osteosarcoma     autophagy     metastasis     drug resistance     Beclin1     LC3B    

标题 作者 时间 类型 操作

Influence and related mechanism of Retn gene expression on glucose uptake in 3T3-L1 cells

LI Yahui, DONG Shiyuan, YU Chao, JIANG Yu, LI Huaixing, SUN Shuhan

期刊论文

Cryo-copolymerization preparation of dextran-hyaluronate based supermacroporous cryogel scaffolds for tissue engineering applications

Dongjiao ZHOU, Shaochuan SHEN, Junxian YUN, Kejian YAO, Dong-Qiang LIN

期刊论文

randomized trials of maintenance bacillus Calmette-Guerin instillation efficacy against recurrence of T1G3

PAN Jiangang, ZHOU Xing, CHEN Zhiguang, HAN Ruifa

期刊论文

CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

null

期刊论文

mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

期刊论文

An extended cell-based smoothed discrete shear gap method (XCS-FEM-DSG3) for free vibration analysis

NGUYEN-THOI,L. Le-ANH,V. Ho-HUU,H. Dang-TRUNG,T. NGUYEN-THOI

期刊论文

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression andhypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1

期刊论文

Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

期刊论文

虞晓含:中医话健康,食补改善免疫力(2020年31日)

2022年04月18日

会议视频

基于玻璃通孔的Ka波段宽带滤波封装天线

方针1,2,张继华1,2,3,高莉彬1,2,陈宏伟1,2,李文磊1,2,梁天鹏1,2,蔡旭东1,2,蔡星周3,贾惟聪3,郭欢3,李勇3

期刊论文

APPLE SUMO E3 LIGASE MDSIZ1 NEGATIVELY REGULATES DROUGHT TOLERANCE

期刊论文

用以产生高纯度涡旋波束的宽带圆极化透射阵

邱靓婕1,2,3,4,李秀萍1,2,3,4,齐紫航1,2,3,4,赵文禹1,2,3,4,黄雨菡5

期刊论文

Self-motions of 3-RPS manipulators

Josef SCHADLBAUER, Manfred L. HUSTY, Stéphane CARO, Philippe WENGERY

期刊论文

APPLE SUMO E3 LIGASE MDSIZ1 NEGATIVELY REGULATES DROUGHT TOLERANCE

期刊论文

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

期刊论文