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UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGcip in hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1856-1868页

作者： Junjie Xu lin Ji Yeling Ruan Zhe wan Zhongjie lin Shunjie Xia Liye Tao Junhao Zheng Liuxin cai Yifan wang Xiao Liang Xiujun cai Key Laboratory of Laparoscopic Technology of Zhejiang Province Department of General SurgerySir Run-Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research center of Severe Hepatobiliary Disease Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and EquipmentHangzhouChina Zhejiang University cancer center HangzhouChina Liangzhu Laboratory Zhejiang University Medical CenterHangzhouChina

The treatment for hepatocellular carcinoma(Hcc)is promising in recent years,but still facing critical *** first targeted therapy,sorafenib,prolonged the overall survival by ***,resistance often occurs,largely limits its *** was found to target the electron transport chain complexes,which results in the generation of reactive oxygen species(ROS).To maintain sorafenib resistance and further facilitate tumor progression,cancer cells develop strategies to overcome excessive ROS production and obtain resistance to oxidative stress-induced cell *** the present study,we investigated the roles of ROS in sorafenib resistance,and found suppressed ROS levels and reductive redox states in sorafenib-resistant Hcc *** in sorafenib-resistant cells maintained greater functional and morphological integrity under the treatment of ***,cellular oxygen consumption rate and mitochondria DNA content analyses revealed fewer numbers of mitochondria in sorafenib-resistant *** investigation attributed this finding to decreased mitochondrial biogenesis,likely caused by the accelerated degradation of peroxisome proliferator-activated receptor y coactivator ip(PGc1P).Mechanistic dissection showed that upregulated UBQLN1 induced PGcip degradation in a ubiquitination-independent manner to attenuate mitochondrial biogenesis and ROS production in sorafenib-resistant cells under sorafenib ***,clinical investigations further indicated that the patients with higher UBQLN1 levels experienced worse recurrence-free *** conclusion,we propose a novel mechanism involving mitochondrial biogenesis and ROS homeostasis in sorafenib resistance,which may offer new therapeutic targets and strategies for Hcc patients.

关键词： homeostasis resistance overcome

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Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes

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World Journal of Gastroenterology 2005年第37期11卷 5821-5827页

作者： Shou-Min Zhu Xue-Feng Ren Jun-Xiang wan Zhao-lin Xia School of Public Health Fu-dan University Shanghai 200032 China

AIM： To analyze occupational health hazards exposure to doses lower than the chinese occupational health standard in a selected Vc polymerization plant in china, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to vinyl chloride monomer （VcM）. METHODS： In order to explore the mechanism of VcM- related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VcM. Genotypes of cYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PcR and PcR-RFLP. RESULTS： Even when the concentration of VcM was lower than the current chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks （RRand 95% c1） were 1.74 （1.06-2.85）, 1.97 （1.56-2.48）, 10.69 （4.38-26.12）, and 2.07 （1.20-3.57）. cYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages （OR 3.29, 95% cI 1.51-7.20, P〈0.01）. cONcLUSION： The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes （cYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1） play important roles in VcM metabolism. Polymorphisms of cYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VcM-induced hepatic damage.

关键词： Vinyl chloride monomer Hepatic lesions cytochrome p450 2E1 Glutathione S-transferase Aldehyde dehydrogenase-2

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circRNA-SORE mediates sorafenib resistance inhepatocellular carcinoma by stabilizing YBX1

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Signal Transduction and Targeted Therapy 2021年第1期6卷 117-130页

作者： Junjie Xu lin Ji Yuelong Liang Zhe wan Wei Zheng Xiaomin Song Kirill Gorshkov Qiming Sun Hui lin Xueyong Zheng Jiang chen Ren-an Jin Xiao Liang Xiujun cai Key Laboratory of Laparoscopic Technology of Zhejiang Province Department of General SurgerySir Run-Run Shaw HospitalZhejiang University School of Medicine310016HangzhouChina Zhejiang University cancer center 310016 HangzhouChina Zhejiang Minimal Invasive Diagnosis and Treantment Thechnology Research center of Severe Hepatobiliary Disease 310016 HangzhouChina National center for Advancing Translational Sciences National Institutes of Health9800 Medical Center DriveBethesdaMD 20892USA State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyChinese Academy of Sciences200031 ShanghaiChina Department of Biochemistry and Department of Cardiology of the Second Affiliated HospitalZhejiang University School of Medicine310058 HangzhouChina

Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(Hcc).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have not been fully *** we report that a circular RNA,circRNA-SORE(a circular RNA upregulated in sorafenib-resistant Hcc cells),plays a significant role in sorafenib resistance in *** found that circRNA-SORE is upregulated in sorafenib-resistant Hcc cells and depletion of circRNA-SORE substantially increases the cell-killing ability of *** studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm,which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 ***,our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among Hcc *** different Hcc mouse models,we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib *** study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in Hcc patients by targeting circRNA-SORE or YBX1.

关键词： sorafenib hepatocellular resistance

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In situ Raman spectroscopic quantification of cH4–cO2 mixture: application to fluid inclusions hosted in quartz veins from the Longmaxi Formation shales in Sichuan Basin, southwestern china

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Petroleum Science 2020年第1期17卷 23-35页

作者： Ye Qiu Xiao-lin wang Xian Liu Jian cao Yi-Feng Liu Bin-Bin Xi wan-Lu Gao School of Earth Sciences and Engineering Nanjing UniversityNanjing 210023JiangsuChina Ocean college Zhejiang UniversityZhoushan 316021ZhejiangChina Wuxi Research Institute of Petroleum Geology SINOPECWuxi 214151JiangsuChina

We re-evaluate the Raman spectroscopic quantification of the molar ratio and pressure for cH4–cO2 ***,the Raman quantification factors of cH4 and cO2 increase with rising pressure at room temperature,indicating that Raman quantification of cH4/cO2 molar ratio can be applied to those fluid inclusions(FIs)with high internal pressure(i.e.,>15 MPa).Secondly,the v1(cH4)peak position shifts to lower wavenumber with increasing pressure at constant temperature,confirming that the v1(cH4)peak position can be used to calculate the fluid ***,this method should be carefully calibrated before applying to FI analyses because large discrepancies exist among the reported v1(cH4)-P curves,especially in the highpressure *** calibrations are applied to cH4-rich FIs in quartz veins of the Silurian Longmaxi black shales in southern Sichuan *** vapor phases of these FIs are mainly composed of cH4 and minor cO2,with cO2 molar fractions from4.4%to 7.4%.The pressure of single-phase gas FI ranges from 103.65 to 128.35 MPa at room temperature,which is higher than previously *** calculations supported the presence of extremely high-pressure cH4-saturated fluid(218.03–256.82 MPa at 200°c),which may be responsible for the expulsion of cH4 to adjacent reservoirs.

关键词： Raman spectroscopy Molar ratio Fluid pressure cO2–cH4 mixture Fluid inclusion Paleo-overpressure

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The complete mitochondrial genome of Odontolabis fallaciosa(coleoptera: Lucanidae) with its phylogenetic implications

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Zoological Systematics 2018年第3期43卷 268-275页

作者： Qian wang Jing Liu Ziqi lin Xia wan Department of Ecology School of Resources and Engineering Anhui University

In this study, the complete mitochondrial genome of Odontolabis fallaciosa was sequenced for the first time using the next generation sequencing method. Like most reported mitogenomes of scarab beetles, it was a double-stranded circular molecule, consisting of 13 protein-coding genes（PcGs）, 22 transfer RNA genes, 2 ribosomal RNA genes, and a control region. The mitogenome of O. fallaciosa was 19,614 bp in length. The base nucleotide composition in the mitogenome of O. fallaciosa was： A（40.0%）, T（30.5%）, c（18.5%） and G（11.0%）, with the total AT content of 70.5%. The phylogenetic analysis of twelve species of stag beetles and other three scarab beetles showed that O. fallaciosa and Aegus angustus share a common ancestor. The mitogenomic data could provide a reliable reference for the future study on conservation, phylogeny and even evolution of these species.

关键词： Mitogenome stag beetle the next generation sequencing phylogenetic analysis

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Biofunctionality Studies of <i>cudrania cochinchinensis</i>Extracts

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American Journal of Analytical chemistry 2018年第1期9卷 1-14页

作者： Wayne c. Liao c.wan-fwu lin chia-ching lin Rui-Fen He chien-chih chen Wen-Ying Huang Department of Nursing Chang Gung University of Science and Technology Chia-Yi Campus Taiwan Department of cosmetic Science Chang Gung University of Science and Technology Tao-Yuan Campus Taiwan Department of Applied cosmetology Hung-Kuang University Taichung Taiwan Department of Biotechnology Hung-Kuang University Taichung Taiwan

cudrania cochinchinensis has been found to show remarkable medicinal values. The total phenolic and flavonoid contents of c. cochinchinensis extracts were analyzed, and the antioxidant activity and reducing ability of c. cochinchinensis extracts were also evaluated. Tetrahydroxyflavanonol (THF) was isolated from the xylem and pith portions of c. cochinchinensis stem;however, the bark portion of c. cochinchinensis stem was found to contain no THF. consequently, solutions extracted from the xylem and pith portions of c. cochinchinensis showed good antioxidant activity. The Ic50 values of pith, xylem, and bark extracts were 0.779, 3.020, and 3.507 mg/mL, respectively. As the pith portion of c. cochinchinensis stem contained more THF and had a higher flavonoid content, it exhibited better antioxidant activity and reducing ability. In addition, c. cochinchinensis pith extracts reduced tyrosinase activity in a dose-dependent manner with Ic50 = 16.1 μg/mL. The inhibitory activity was determined to be noncompetitive with Km = 0.23 mM.

关键词： cudrania cochinchinensis Tetrahydroxyflavanonol Antioxidant Activity Reducing Ability Tyrosinase

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稳心颗粒对心房颤动患者心脏结构重构及炎症因子影响的Meta分析

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药物评价研究 2024年第9期47卷 2130-2146页

作者：齐葭杨志飞汪吴娇薄敏敏武玉泽郭伶俐林谦万洁北京中医药大学北京100029 北京中医药大学东方医院心内科北京100078 北京中医药大学东直门医院心内科北京100070 北京市朝阳区中医医院内科北京100020

目的通过Meta分析的方法评价稳心颗粒对房颤患者心脏结构重构及炎症因子的影响。方法检索PubMed、Embase、cochrane Library、Web of Science、中国学术期刊全文数据库(cNKI)、万方数据库(wanfang Data)、中国生物医学文献数据库(cBM)... 详细信息

目的通过Meta分析的方法评价稳心颗粒对房颤患者心脏结构重构及炎症因子的影响。方法检索PubMed、Embase、cochrane Library、Web of Science、中国学术期刊全文数据库(cNKI)、万方数据库(wanfang Data)、中国生物医学文献数据库(cBM)、维普生物医学数据库(VIP)中稳心颗粒治疗房颤的临床随机对照试验(RcTs);使用Excel录入文献基本信息;使用RevMan 5.4进行质量评价、异质性检验及森林图绘制;使用StataMP 17.0进行漏斗图绘制及Egger检验。结果共纳入39项RcTs,包含4211例研究对象。Meta分析结果显示:稳心颗粒可提高房颤患者左室射血分数(LVEF,MD=6.01,95%置信区间(cI)[5.03,6.99],PcI[-7.66,-5.04],PcI[-4.80,-3.90],PcI[-5.43,-1.83],Pc反应蛋白(hs-cRP,MD=-2.28,95%cI[-3.07,-1.48],Pc反应蛋白(cRP,MD=-5.71,95%cI[-6.62,-4.79],PcI[-17.00,-3.74],P=0.002)、基质金属蛋白酶-9(MMP-9,MD=-23.27,95%cI[-26.42,-20.11],PcI[-90.44,-21.27],P=0.002),其差异具有统计学意义。试验组不良反应发生率低于对照组(RR=0.74,95%cI[0.59,0.93],P=0.009),其差异具有统计学意义。结论稳心颗粒可改善房颤患者结构重构指标、降低炎症因子,且安全性较好。

关键词：稳心颗粒心房颤动结构重构炎症 Meta分析

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多级孔铁氮掺杂生物炭催化剂的制备及性能

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化工环保 2024年第4期44卷 546-553页

作者：林逸宁葛强万金泉朱丛韵王艳周贤波刘宽勇刘和芳华南理工大学环境与能源学院广东广州510006 中国轻工业长沙工程有限公司湖南长沙410114 华南理工大学制浆造纸工程国家重点实验室广东广州510640 贵州鹏昇(集团)纸业有限责任公司贵州黔西南552401

在水稻秸秆基铁氮掺杂生物炭粉末催化剂的基础上,制备了多级孔铁氮掺杂生物炭成型固体催化剂,探讨了其成型工艺,对其进行了表征,并对其活化过硫酸盐降解有机污染物的性能进行了评价,为铁氮掺杂生物炭催化剂的工业放大提供参考。该方法... 详细信息

在水稻秸秆基铁氮掺杂生物炭粉末催化剂的基础上,制备了多级孔铁氮掺杂生物炭成型固体催化剂,探讨了其成型工艺,对其进行了表征,并对其活化过硫酸盐降解有机污染物的性能进行了评价,为铁氮掺杂生物炭催化剂的工业放大提供参考。该方法制备的成型球体催化剂具有良好的力学性能、丰富的多级孔结构、极低的铁离子浸出,可在宽pH范围内有效去除实际废水cOD以及三氯苯酚(TcP)、双酚A(BPA)等有机污染物,可通过浸渍和热处理再生。吸附60 min、降解100 min后,cOD、TcP、BPA的去除率分别可达46.85%、63.62%、90.18%。Fe^(2+)、Fe^(0)能够活化过硫酸盐产生·OH、SO_(4)^(-)·、·O_(2)^(-)和^(1)O_(2)降解有机污染物,Fe—N、c=O、O=c—OH和π→π^(*)位点作为电子供体,氧化态N作为电子受体。

关键词：铁氮掺杂生物炭催化剂成型过硫酸盐高级氧化造孔

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全新世安达曼海周边区域火灾历史及其影响因素

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地球科学进展 2024年第6期39卷 616-631页

作者：梁诗晴罗传秀向荣 ARIFUL Islam 魏海成苏翔万随杜恕环张兰兰杨艺萍黄云林刚中国科学院南海海洋研究所中国科学院边缘海与大洋地质重点实验室广东广州510301 中国科学院大学北京100049 中国科学院青海盐湖研究所青海省盐湖地质与环境重点实验室青海西宁810008 丹麦技术大学丹麦罗斯基勒4000

火事件的发生与气候变化以及植被变化密切相关,系统性地研究全新世火活动的时空演化规律,可以更清晰地理解火活动机制与区域性气候、植物变化的关联,同时有助于预测未来火的演化趋势。为了解安达曼海周边地区火灾活动的演化以及可能的... 详细信息

火事件的发生与气候变化以及植被变化密切相关,系统性地研究全新世火活动的时空演化规律,可以更清晰地理解火活动机制与区域性气候、植物变化的关联,同时有助于预测未来火的演化趋势。为了解安达曼海周边地区火灾活动的演化以及可能的驱动因素,以安达曼海南部的海洋钻孔ADM-c1为研究材料,对其全新世以来的炭屑记录进行深入分析,并综合安达曼海周边地区其余的5个炭屑记录,重建了全新世以来安达曼海周边地区火灾活动的演变过程。研究表明,尽管点火、火灾天气和植被组成在各地不尽相同,导致火灾发生频率在区域和地方范围有所不同,但在广泛的气候变化背景下,全新世安达曼海周边各地的火事件发生频率变化具有广泛同步性。全新世安达曼海周边的火灾活动发生频率受到区域性植被和降水变化影响,并最终受控于印度夏季风强度的变化。与末次冰消期相比,12.0~9.0 ka BP安达曼海周边区域火灾活动的发生频率呈下降趋势,反映了印度夏季风降水逐步增加以及木本植物含量逐渐上升的区域环境;9.0~5.0 ka BP较低的区域火灾活动发生频率同时受到较高的印度夏季风降水量和区域木本植物含量的制约;5.0 ka BP后高频的区域火灾活动更多反映了印度夏季风降水的降低。此外,研究结果还表明全新世安达曼海周边区域火灾活动发生频率与厄尔尼诺—南方涛动强度、印度洋偶极子位相和热带辐合带位置的变化相关。

关键词：炭屑古火印度夏季风全新世安达曼海

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Identification and characterization of a monoclonal antibody blocking the SARS-coV-2 spike protein–AcE2 interaction

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cellular & Molecular Immunology 2021年第6期18卷 1562-1564页

作者： MengYa Yuan YaoYing wan cui Liu Yue Li\ZhaoYuan Liu changDong lin JianFeng chen State Key Laboratory of cell Biology Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina

Because cOVID-19 has spread as a global pandemic,the development of therapeutics for this disease,such as neutralizing antibodies that can efficiently block SARS-coV-2 infection,is urgently *** the infection of host cells by SARS-coV-2,the spike(S)glycoprotein of SARS-coV-2 plays the most crucial roles in viral entry and cell *** S protein includes two components,the S1 and S2 *** S1 subunit is vital in determining tissue tropism and host ranges and consists of the N-terminal domain and c-terminal receptor-binding domain(RBD).1,2 Of note,the RBD of the S protein(S-RBD)supports the binding of the S protein to angiotensin-converting enzyme 2(AcE2)on host cells,contributing to cell entry by SARS-coV-2.3 Therefore,the S-RBD is widely used for the development of neutralizing antibodies,small-molecule inhibitors and vaccines.

关键词： AcE2 monoclonal infection

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