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Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

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Chinese Medical Journal 2024年第2期137卷 209-221页

作者： Shi Qiu Yaqi Qiu Linghui Deng Ling Nie Liming Ge Xiaonan Zheng Di Jin Kun Jin Xianghong Zhou Xingyang Su Boyu Cai Jiakun Li Xiang Tu Lina Gong Liangren Liu Zhenhua Liu Yige Bao Jianzhong Ai Tianhai Lin Lu Yang Qiang Wei Department of Urology Institute of UrologyNational Clinical Research Center for Geriatrics and Center of Biomedical Big DataWest China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Molecular Oncology Institute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland Department of Science and Drug Technology University of TurinTurinItaly National Clinical Research Center of Geriatrics The Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610000China Department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pharmaceutics and Bioengineering School of Chemical EngineeringSichuan UniversityChengduSichuan 610000China

Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types.Nonetheless,the existence of soft tumor cells in bladder tumors remains elusive.Thus,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor cells.Expression patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western blotting.Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.Results:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer cells.More importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor relapse.Furthermore,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells.Simultaneously,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness.Meanwhile,the soft tumor cells become more sensitive to chemotherapy after stiffening,that offers new insights fo

关键词： Soft tumor cells 3D Matrigel Stemness Non-muscle invasive bladder neoplasms Microfluidic analytical techniques

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Cellular mechanotransduction in health and diseases:from molecular mechanism to therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3705-3736页

作者： Xingpeng Di Xiaoshuai Gao Liao Peng Jianzhong Ai Xi Jin Shiqian Qi Hong Li Kunjie Wang Deyi Luo Department of Urology and Institute of Urology National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduP.R.China State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengduP.R.China

Cellular mechanotransduction,a critical regulator of numerous biological processes,is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism.Typical mechanical cues in organisms include hydrostatic pressure,fluid shear stress,tensile force,extracellular matrix stiffness or tissue elasticity,and extracellular fluid viscosity.Mechanotransduction has been expected to trigger multiple biological processes,such as embryonic development,tissue repair and regeneration.However,prolonged excessive mechanical stimulation can result in pathological processes,such as multi-organ fibrosis,tumorigenesis,and cancer immunotherapy resistance.Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified,the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated,and no effective therapies are currently available targeting mechanical cue-related signaling.This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence.The key effectors responding to mechanical stimulations are listed,such as Piezo channels,integrins,Yes-associated protein(YAP)/transcriptional coactivator with PDZ-binding motif(TAZ),and transient receptor potential vanilloid 4(TRPV4).We also reviewed the key signaling pathways,therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.

关键词： diseases stimulation therapeutic

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DOK3 promotes proliferation and inhibits apoptosis of prostate cancer via the NF-κB signaling pathway

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Chinese Medical Journal 2023年第4期136卷 423-432页

作者： Kun Jin Shi Qiu Bo Chen Zilong Zhang Chichen Zhang Xianghong Zhou Lu Yang Jianzhong Ai Qiang Wei Department of Urology and National Clinical Research Center for Geriatrics West China HospitalSichuan UniversityChengduSichuan 610041China Center of Biomedical Big Data West China HospitalSichuan UniversityChengduSichuan 610041China Department of Urology and Institute of Urology West China HospitalSichuan UniversityChengduSichuan 610041China

Background: DOK3 (Downstream of kinase 3) is involved primarily with immune cell infiltration. Recent research reported the role of DOK3 in tumor progression, with opposite effects in lung cancer and gliomas;however, its role in prostate cancer (PCa) remains elusive. This study aimed to explore the role of DOK3 in PCa and to determine the mechanisms involved. Methods: To investigate the functions and mechanisms of DOK3 in PCa, we performed bioinformatic and biofunctional analyses. Samples from patients with PCa were collected from West China Hospital, and 46 were selected for the final correlation analysis. A lentivirus-based short hairpin ribonucleic acid (shRNA) carrier was established for silencing DOK3. A series of experiments involving the cell counting kit-8, bromodeoxyuridine, and flow cytometry assays were performed to identify cell proliferation and apoptosis. Changes in biomarkers from the nuclear factor kappa B (NF-κB) signaling pathway were detected to verify the relationship between DOK3 and the NF-κB pathway. A subcutaneous xenograft mouse model was performed to examine phenotypes after knocking down DOK3 in vivo . Rescue experiments with DOK3 knockdown and NF-κB pathway activation were designed to verify regulating effects. Results: DOK3 was up-regulated in PCa cell lines and tissues. In addition, a high level of DOK3 was predictive of higher pathological stages and worse prognoses. Similar results were observed with PCa patient samples. After silencing DOK3 in PCa cell lines 22RV1 and PC3, cell proliferation was significantly inhibited while apoptosis was promoted. Gene set enrichment analysis revealed that DOK3 function was enriched in the NF-κB pathway. Mechanism experiments determined that knockdown of DOK3 suppressed activation of the NF-κB pathway, increased the expressions of B-cell lymphoma-2 like 11 (BIM) and B-cell lymphoma-2 associated X (BAX), and decreased the expression of phosphorylated-P65 and X-linked inhibitor of apoptosis (XIAP). In the rescue experiments, pharmacological activat

关键词： Prostate cancer Downstream of kinase 3 Prognosis Nuclear factor kappa B

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回顾性分析电解白发联合毛囊移植治疗25例毛发部位白癜风的疗效

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中华皮肤科杂志 2024年第1期57卷 46-49页

作者：王涛武毅靳虹戴叶芹彭建中许爱娥宋秀祖杭州市第三人民医院皮肤科杭州310009

目的总结睫毛电解器电解白发联合毛囊移植治疗毛发部位白癜风的临床疗效.方法回顾性分析2019年1月至2021年1月杭州市第三人民医院皮肤外科收治的25例稳定期白癜风伴毛发色素脱失患者的临床资料.所有患者均采用睫毛电解器电解白发联合... 详细信息

目的总结睫毛电解器电解白发联合毛囊移植治疗毛发部位白癜风的临床疗效.方法回顾性分析2019年1月至2021年1月杭州市第三人民医院皮肤外科收治的25例稳定期白癜风伴毛发色素脱失患者的临床资料.所有患者均采用睫毛电解器电解白发联合毛囊移植治疗病损处白发.术后1周、1个月、3个月、6个月门诊随访,观察移植毛发质地及生长情况,并记录移植毛囊成活率及新生白发率.结果 25例稳定期白癜风患者中,男14例,女11例,病程2~15年,平均5.8年.共30处病损,位于头皮9处,眉毛7处,睫毛14处.术后1周所有患者移植毛发存活良好,未见明显脱落,无局部感染.术后6个月原病损区毛发基本复色,仅有少许白发新生,未见明显瘢痕形成;移植毛囊成活率76.5%±10.0%,白发新生率16.7%±7.8%.结论睫毛电解器电解白发联合毛囊移植治疗毛发部位白癜风,过程简单易行,疗效较好,且术后并发症少,为临床治疗毛发部位白癜风提供可靠的选择.

关键词：白癜风毛发去除头皮眉毛睫毛毛囊移植电解器

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冲击荷载作用下钢管再生混凝土柱损伤评估分析

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振动与冲击 2024年第12期43卷 97-108页

作者：陈华艳刘用滨罗才松黄建忠许力付朝江祁皑福建理工大学福建省土木工程新技术与信息化重点实验室福州350118 福州大学土木工程学院福州350116

为研究钢管再生混凝土柱在冲击荷载作用下的损伤,进行了16根钢管再生混凝土柱的落锤冲击试验。在试验的基础上建立了钢管再生混凝土柱的有限元模型,分析不同冲击速度、冲击质量、截面含钢率对钢管再生混凝土柱损伤程度的影响。通过控制... 详细信息

为研究钢管再生混凝土柱在冲击荷载作用下的损伤,进行了16根钢管再生混凝土柱的落锤冲击试验。在试验的基础上建立了钢管再生混凝土柱的有限元模型,分析不同冲击速度、冲击质量、截面含钢率对钢管再生混凝土柱损伤程度的影响。通过控制冲击质量与冲击速度,基于损伤因子d_(s)和弹塑性转角θ,划分损伤评估等级,拟合钢管再生混凝土柱损伤评估曲线。结果表明:建立的有限元模型能很好地吻合落锤冲击试验的结果,最大误差不超过10%;冲击过程中跨中挠度峰值出现时间远远滞后于冲击力峰值出现的时间,冲量是动量的1.23倍;随着冲击速度的增加,跨中挠度呈抛物线形的增长趋势,冲击质量增加对冲击力峰值影响较小,但对跨中挠度有较大影响,随着截面含钢率的增加,构件的耗能几乎稳定在90%附近;从损伤曲线图可以快速判断钢管再生混凝土柱的整体损伤情况及局部损伤情况。

关键词：钢管再生混凝土柱落锤冲击有限元模拟冲击能量损伤评估

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含油污泥和泥饼掺混焚烧处置研究

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山东化工 2024年第10期53卷 262-265页

作者：章爱费宇航李宁辉李小龙朱建中郭琳琳纵瑞耘中海油节能环保服务有限公司天津300457

为了解决含油污泥给环境要素带来危害。另外,泥饼若不能及时处理,不仅占据大量土地空间,还会散发异味,不利于作业人员身心健康。为此,采用焚烧处理技术对含油污泥和泥饼混合物进行处理,可以得出:含油污泥的有机相更丰富,泥饼的含水率更... 详细信息

为了解决含油污泥给环境要素带来危害。另外,泥饼若不能及时处理,不仅占据大量土地空间,还会散发异味,不利于作业人员身心健康。为此,采用焚烧处理技术对含油污泥和泥饼混合物进行处理,可以得出:含油污泥的有机相更丰富,泥饼的含水率更低。通过分析热值随含水率变化的情况,发现含水率越高,热值越低,控制在30%~50%更合适。此外,在不同掺混比例条件下观察锅炉温度随时间的变化情况,当质量比为1∶4时,能满足焚烧的热值和含水率的要求,同时热值提升了15%。通过对比前年的线监测数据发现,污泥掺混能很好地控制工艺和维持数据的稳定。

关键词：含油污泥泥饼掺混焚烧

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Bispectrum Feature Extraction of Gearbox Faults Based on Nonnegative Tucker3 Decomposition with 3D Calculations

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Chinese Journal of Mechanical Engineering 2013年第6期26卷 1182-1193页

作者： WANG Haijun XU Feiyun ZHAO Jun’ai JIA Minping HU jianzhong HUANG Peng School of Mechanical Engineering Southeast University

Nonnegative Tucker3 decomposition（NTD） has attracted lots of attentions for its good performance in 3D data array analysis. However, further research is still necessary to solve the problems of overfitting and slow convergence under the anharmonic vibration circumstance occurred in the field of mechanical fault diagnosis. To decompose a large-scale tensor and extract available bispectrum feature, a method of conjugating Choi-Williams kernel function with Gauss-Newton Cartesian product based on nonnegative Tucker3 decomposition（NTD_EDF） is investigated. The complexity of the proposed method is reduced from o（nNlgn） in 3D spaces to o（RiR2nlgn） in 1D vectors due to its low rank form of the Tucker-product convolution. Meanwhile, a simultaneously updating algorithm is given to overcome the overfitting, slow convergence and low efficiency existing in the conventional one-by-one updating algorithm. Furthermore, the technique of spectral phase analysis for quadratic coupling estimation is used to explain the feature spectrum extracted from the gearbox fault data by the proposed method in detail. The simulated and experimental results show that the sparser and more inerratic feature distribution of basis images can be obtained with core tensor by the NTD EDF method compared with the one by the other methods in bispectrum feature extraction, and a legible fault expression can also be performed by power spectral density（PSD） function. Besides, the deviations of successive relative error（DSRE） of NTD_EDF achieves 81.66 dB against 15.17 dB by beta-divergences based on NTD（NTD_Beta） and the time-cost of NTD EDF is only 129.3 s, which is far less than 1 747.9 s by hierarchical alternative least square based on NTD （NTD_HALS）. The NTD_EDF method proposed not only avoids the data overfitting and improves the computation efficiency but also can be used to extract more inerratic and sparser bispectrum features of the gearbox fault.

关键词： nonnegative tucker3 decomposition Tucker-product convolution power spectrum density updating algorithm

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Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma

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Signal Transduction and Targeted Therapy 2022年第3期7卷 896-908页

作者： Yiyi Xi Yuan Lin Wenjia Guo Xinyu Wang Hengqiang Zhao Chuanwang Miao Weiling Liu Yachen Liu Tianyuan Liu Yingying Luo Wenyi Fan ai Lin Yamei Chen Yanxia Sun Yulin Ma Xiangjie Niu Ce Zhong Wen Tan Meng Zhou jianzhong Su Chen Wu Dongxin Lin Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Beijing Advanced Innovation Center for Genomics Biomedical Pioneering Innovation CenterPeking UniversityBeijing 100871China Cancer Institute Affiliated Cancer Hospital of Xinjiang Medical UniversityUrumqi 830000China School of Biomedical Engineering School of Ophthalmology and Optometry and Eye HospitalWenzhou Medical UniversityWenzhou 325011China Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China CAMS Key Laboratory of Genetics and Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma(ESCC),which if diagnosed at advanced stages has<30%five-year survival rate.Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues,we identified 35,577 differentially methylated CpG sites(DMCs)and characterized their distribution patterns.

关键词： esophageal squamous diagnosis

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Effect of aluminum on microstructure and magnetic properties of sintered Nd-Fe-B magnets processed by grain boundary diffusion of Tb-Al

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Journal of Rare Earths 2023年第5期41卷 705-712,I0003页

作者： Tinghui Wang Zhaokun Ma Qihang Zhu Lijing Yang Baosheng Liu Yu Zhao Cheng Xu Bizhang Zheng Fangqin Hu jianzhong Li Qingfang Huang Zhenlun Song CAS Key Laboratory of Magnetic Materials and Devices Zhejiang Province Key Laboratory of Magnetic Materials and Application TechnologyNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China College of Materials Science and Engineering Taiyuan University of Science and TechnologyTaiyuan 030024China Baotou Hidyree Technology Co. Ltd.Baotou 014030China Hangzhou Permanent Magnet Group Co. Ltd.Hangzhou 311231China Ningbo Permanent Magnetics Co. Ltd.Ningbo 315201China Fujian Key Laboratory for Rare Earth Functional Materials Longyan 366300China

The grain boundary diffusion process(GBDP)of Tb can improve the coercivity of sintered Nd-Fe-B magnets.In this study,the effect of ai on the diffusion of Tb in the GBDP was investigated.The content of diffused Tb-Al was precisely controlled by adjusting the magnetron sputtering process.The Tb equivalent of Al was also studied.Results show that ai promotes the diffusion of Tb deeper into the magnet,reducing the thickness of the shell in the core-shell structure.This study is helpful for further developing the process,reducing the consumption of heavy rare earth elements(Tb),and improving the coercivity of sintered Nd-Fe-B magnets.

关键词： Sintered Nd-Fe-Bmagnet Heavy rare earth elements Grain boundary diffusion process Coercivity

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Methods and Effects of Hongshan Cock Spermatozoa Cryopreservation

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Wuhan University Journal of Natural Sciences 2006年第2期11卷 447-450页

作者： LIU jianzhong ZHANG Yiling College of Chemical Engineering and Technology Wuhan University of Science and Technology Wuhan 430081 Hubei China College of Animal Science and Technology Northwestern University of Science and Technology in Agriculture and Forest Yangling 712100 Shannxi China

The survival rates, acrosomic integrity rates of frozen semen from Hongshan cock and fertilities of the frozen-thawed spermatozoa in both pellets and straws were studied. The result shows that the average survival rate of spermatozoa in straws was 0, 451±0, 056, and 0. 390±0. 040 in pellets, the former was significantly higher than the later （n=20, p〈0, 01）, The average acrosomic integrity rate of the sperms was 0, 613±0. 049 in straws, and 0. 476±0. 057 in pellets. The former was significantly higher than the later （n= 20, p〈0.05）. The fertility rates （%） of sperms in pellets, straws and freshly colleered semen at the third day after artificial insemination （ai） were 85.32±2. 32, 87. 73±1.00 and 90.77±1.68, respectively. The fertility rate,s of the three types of semen at the fourth and fifth days were lower than the third day＇s. Variance analysts shows that the fertilities of the spermatozoa in pellets and straws were significantly lower than freshly collected semen （n=3, p〈0.01）, and the fertilities of the spermatozoa in straws were significantly higher than those in pellets （n= 3, p〈0.01）.

关键词： Hongshan cock ,spermatozoa cryopreservation fertilities

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