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Science China(Life Sciences) 2014年第10期57卷 998-1010页

作者： LI Xiang ZHAO KaiDi guo wenjie LIU Xu LIU Jia GAO Jing CHEN QiuYun BAI YiDong School of Pharmacy Jiangsu University School of Chemistry & Chemical Engineering Jiangsu University Department of Cellular and Structural Biology University of Texas Health Science Center at San Antonio

We previously identified a novel synthesized metal compound, LMnAc （[L2Mn2（Ac）（H20）e]（Ac）（L=bis（2-pyridylmethyl） amino-2-propionic acid））. This compound exhibited significant inhibition on cancer cell proliferation and was more selective against cancer cells than was the popular chemotherapeutic reagent cisplatin. In this study, we further investigated the underlying molecular mechanisms of LMnAc-induced cancer cell death. We found that LMnAc achieved its selectivity against cancer cells through the transferrin-transferrin receptor system, which is highly expressed in tumor cells. LMnAc triggered cancer cells to commit autophagy and apoptosis, which was mediated by the mitochondrial pathway. Moreover, LMnAc disrupted mitochondrial function, resulting in mitochondrial membrane potential collapse and ATP reduction. In addition, LMnAc induced intracellular Ca^2＋ overload and reactive oxygen species generation. Interestingly, its anticancer effect was significantly reduced following pretreatment with the antioxidant N-acetyl cysteine, indicating that reactive oxygen species triggered cell death. Altogether, our data suggest that LMnAc appears to be a selectively promising anticancer drug candidate.

关键词： Mn(II) complex selective antitumor autophagy apoptosis mitochondria ROS

DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS-STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

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Acta Pharmaceutica Sinica B 2022年第1期12卷 262-273页

作者： Yuanyuan Wang Bin Wei Danping Wang Jingjing Wu Jianhua Gao Haiqing Zhong Yang Sun Qiang Xu Wen Liu Yanhong Gu wenjie guo Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Cancer Rehabilitation Center Jiangsu Province HospitalNanjing 210029China Department of Oncology the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical UniversityHuai'an 223300China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan(CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA(ds DNA) from the intestine, leading to cyclic-GMP-AMP synthase(c GAS)-stimulator of interferon genes(STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination(HR) repair and downregulate ds DNA-c GAS-STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

关键词： CPT-11 Gastrointestinal mucositis Andrographolide Homologous recombination cGAS-STING

SHP2-mediated mitophagy boosted by lovastatin in neuronal cells alleviates parkinsonism in mice

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Signal Transduction and Targeted Therapy 2021年第2期6卷 251-253页

作者： Wen Liu Meijing Wang Lihong Shen Yuyu Zhu Hongyue Ma Bo Liu Liang Ouyang wenjie guo Qiang Xu Yang Sun State Key Laboratory of Pharmaceutical Biotechnology Department of Biotechnology and Pharmaceutical SciencesSchool of Life SciencesNanjing UniversityNanjingChina Jiangsu Key Laboratory of Efficacy and Safety Evaluation of TCM Nanjing University of Chinese MedicineNanjingChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengduChina Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University209 Tongshan RoadXuzhouJiangsuChina Chemistry and Biomedicine Innovation Center(ChemB/C) Nanjing UniversityNanjingChina

Dear Editor,The loss of PINK1/Parkin-dependent mitochondrial clearance causes loss of dopaminergic neurons in the substantia nigra and contributes to the pathogenesis of Parkinson's disease(PD).Several kinases were reported to regulate the ubiquitin E3 ligase activity of Parkin through phosphorylation but the involvement of protein tyrosine phosphatase(PTPase)for Parkin activity remains elusive.

关键词： PINK1 Parkin lovastatin

基于工况分类的熟料f-CaO含量预测方法研究

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水泥工程 2024年第1期 1-5,15页

作者：崔保华张成伟李慧霞陈克政郭文洁孙战军中材国际智能科技有限公司江苏南京210036 洛阳黄河同力水泥有限责任公司河南洛阳471600

为实现游离氧化钙(f-CaO)含量的持续稳定预测,采用集成学习算法研究软测量实现方法。针对烧成系统中的复杂工况,首先展开工况分类,然后对每一类工况构建集成学习预测模型,同时引入在线建模的方式提高模型的泛化能力和时间有效性,解决了... 详细信息

为实现游离氧化钙(f-CaO)含量的持续稳定预测,采用集成学习算法研究软测量实现方法。针对烧成系统中的复杂工况,首先展开工况分类,然后对每一类工况构建集成学习预测模型,同时引入在线建模的方式提高模型的泛化能力和时间有效性,解决了模型短期有效和重复性建模的问题。集成学习算法基于bagging的思想进行对多种弱学习器构建模型,通过检验发现模型效果显著优于单一模型效果。该算法融合了工艺生产特点和多种回归算法,具有较好的稳定性和提前性,实现了水泥质量的实时控制,助力水泥厂高质量稳定生产。

关键词： f-CaO 集成学习软测量工况分类在线建模

辽东楤木总皂苷联合酵母硒对C57小鼠的降血糖作用

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养殖与饲料 2024年第10期23卷 29-32页

作者：李欣徐赫临李文超李康李美琪张莹郭文洁沈阳工学院生命工程学院辽宁抚顺113122

[目的]探究辽东楤木总皂苷联合酵母硒对2型糖尿病小鼠血糖的影响,为研制治疗糖尿病的新药物提供参考。[方法]选用60只C57小鼠,10只为对照组(A组),其余采用30 mg/kg链脲佐菌素建立糖尿病模型作为试验组。建模成功后随机分成B、C、D、E、F... 详细信息

[目的]探究辽东楤木总皂苷联合酵母硒对2型糖尿病小鼠血糖的影响,为研制治疗糖尿病的新药物提供参考。[方法]选用60只C57小鼠,10只为对照组(A组),其余采用30 mg/kg链脲佐菌素建立糖尿病模型作为试验组。建模成功后随机分成B、C、D、E、F组,即模型组、二甲双胍组、辽东楤木总皂苷+酵母硒(120 mg/kg+1.5 mg/kg)组、辽东楤木总皂苷+酵母硒(120 mg/kg+1.0 mg/kg)组、辽东楤木总皂苷+酵母硒(120 mg/kg+0.5 mg/kg)组,每组各10只,连续治疗4周,采用血糖仪、全自动糖化血红蛋白分析仪、全自动生化分析仪对C57小鼠尾静脉血液中空腹血糖、糖化血红蛋白、血脂、口服葡萄糖耐量进行检测。[结果]与B组相比,各试验组均有不同程度的变化,C组、D组优于其他各组,且二组之间差异不显著。D组FBG降低了4.86 mmol/L,HbA1c水平下降了3.87%,TC、TG和LDL水平分别下降了1.18、0.02、1.72 mmol/L,而HDL显著升高0.42 mmol/L。口服糖耐量检测2 h恢复至餐前水平。[结论]120 mg/kg辽东楤木总皂苷联合1.5 mg/kg酵母硒降血糖效果最佳。

关键词：辽东楤木总皂苷酵母硒降血糖作用小鼠 2型糖尿病

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Reconfigurable logic and in-sensor encryption operations in an asymmetrically tunable van der Waals heterostructure

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Nano Research 2024年第4期17卷 3113-3119页

作者： Fan Gong wenjie Deng Yi Wu Fengming Liu Yihao guo Zelin Che Jingjie Li Jingzhen Li Yang Chai Yongzhe Zhang Key Laboratory of Optoelectronics Technology of Education Ministry of China Faculty of Information TechnologyBeijing University of TechnologyBeijing 100124China Key Laboratory of Advanced Functional Materials Ministry of EducationFaculty of Materials and ManufacturingBeijing University of TechnologyBeijing 100124China Department of Applied Physics Hong Kong Polytechnic UniversityKowloonHong KongChina

Reconfigurable devices can be used to achieve multiple logic operation and intelligent optical sensing with low power consumption,which is promising candidates for new generation electronic and optoelectronic integrated ***,the versatility is still limited and need to be extended by the device architectures ***,we report an asymmetrically gate two-dimensional(2D)van der Waals heterostructure with hybrid dielectric layer SiO_(2)/hexagonal boron nitride(h-BN),which enable rich function including reconfigurable logic operation and in-sensor information encryption enabled by both volatile and non-volatile optoelectrical *** the partial gate is grounded,the non-volatile light assisted electrostatic doping endowed partially reconfigurable doping between n-type and p-type,which allow the switching of logic XOR and not implication(NIMP).When the global gate is grounded,additionally taking the optical signal as another input signal,logic AND and OR is realized by combined regulation of the light and localized gate *** on the high on/off current ratio approaching 105 and reliable&switchable logic gate,in-sensor information encryption and decryption is demonstrated by manipulating the logic ***,these results provide strong extension for current reconfigurable electronic and optoelectronic devices.

关键词： in-sensor encryption reconfigurable logic van der Waals heterostructure asymmetrical tunable architecture

有限长圆柱壳-流场部分耦合系统声振建模及机理研究

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振动与冲击 2022年第15期41卷 43-53页

作者：郭文杰杨舟华东交通大学交通运输工程学院南昌330013

圆柱壳-流场部分耦合系统(圆柱壳轴线与自由液面平行)在工程中广泛应用,其声振性能关系到结构的安全性、功能性;此外,流体负载在结构周向分布的非连续性,以及自由液面的声波反射效应会对声固耦合振动产生交互影响,其中又含有丰富的学术... 详细信息

圆柱壳-流场部分耦合系统(圆柱壳轴线与自由液面平行)在工程中广泛应用,其声振性能关系到结构的安全性、功能性;此外,流体负载在结构周向分布的非连续性,以及自由液面的声波反射效应会对声固耦合振动产生交互影响,其中又含有丰富的学术问题。因此,开展对圆柱壳-流场部分耦合系统的声振研究工作。首先,以有限长部分浸没圆柱壳为研究对象,基于声场、结构两套不同坐标系建立了系统的数学物理模型;然后利用Galerkin法处理声固耦合面上振速连续条件,得到声场和位移场系数向量的矩阵关系,进而可对振动量进行理论求解。与有限元结果对比验证了该方法的准确性,且该方法具有适用范围广、计算量小的优势。接着,将方法延拓到处理部分充液工况,且对比研究了相同液面高度下部分充液圆柱壳与部分浸没圆柱壳自振特性的异同,并从数学机理上揭示了其成因。

关键词：部分浸没圆柱壳部分充液圆柱壳两套坐标系 Galerkin法声固耦合振动

Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis

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Journal of Molecular Cell Biology 2020年第4期12卷 277-290页

作者： Mingxia Zhao Lihong Shen Zijun Ouyang Manru Li guoliang Deng Chenxi Yang Wei Zheng Lingdong Kong Xuefeng Wu Xudong Wu wenjie guo Ye Yin Qiang Xu Yang Sun State Key Laboratory of Pharmaceutical Biotechnology Department of Biotechnology and Pharmaceutical SciencesSchool of Life SciencesNanjing UniversityNanjing 210023China Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing 210029China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Impairment of glucose(Glu)uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic *** nuclear ribonucleoprotein A1(hnRNP Al)is a highly abundant RNA-binding protein that has been implicated in diverse cellular *** aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu *** results showed that conditional deletion of hnRNP Al in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet(HFD).Conditional knockout mice fed a HFD showed exacerbated obesity,insulin resistance,and hepatic *** vitro interference of hnRNP Al in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake,whereas hnRNP Al overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of *** expression and stability of glycogen synthase(gysl)mRNA were also decreased in the absence of hnRNP A ***,hnRNP Al interacted with gys l and stabilized its mRNA,thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle *** together,our findings are the first to show that reduced expression of hnRNP Al in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis.

关键词： hnRNP A1 insulin resistance hepatic steatosis glycogen synthesis

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

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Acta Pharmaceutica Sinica B 2019年第2期9卷 304-315页

作者： Mingxia Zhao wenjie guo Yuanyuan Wu Chenxi Yang Liang Zhong guoliang Deng Yuyu Zhu Wen Liu Yanhong Gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun State Key Laboratory of Pharmaceutical Biotechnology Deparment of Biotechnology and Pharmaceutical Sciences School of Life Sciences Nanjing University Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Natural and Biomimetic Drugs Department of Chemical Biology School of Pharmaceutical Sciences Peking University Department of Oncology the First Affiliated Hospital with Nanjing Medical University

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to ***, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune ***099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

关键词： Cancer immunotherapy SHP2 SHP099 PD-1 Colon cancer

Enhancing the peroxidase-like activity of MoS_(2)-based nanozymes by introducing attapulgite for antibacterial application and sensitive detection of glutathione

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Nano Research 2024年第8期17卷 7415-7426页

作者： Feng Feng Yihe Zhang Xiao Zhang Bin Mu Jiahe Zhang wenjie Qu Wangshu Tong Minmin Liang Qi An Zhanjun guo Lu Zhao Engineering Research Center of Ministry of Education for Geological Carbon Storage and Low Carbon Utilization of Resources Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid WastesNational Laboratory of Mineral MaterialsSchool of Materials Science and TechnologyChina University of Geosciences(Beijing)Beijing 100083China Key Laboratory of Clay Mineral Applied Research of Gansu Province Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000China Experimental Center of Advanced Materials School of Materials Science and Engineering School of Materials Science and EngineeringBeijing Institute of TechnologyBeijing 100081China

Nanozymes are next-generation of nanomaterials with enzyme-like *** particular,nanozymes with peroxidase(POD)-like activity have been utilized in various fields,including antibacterial,detection,degradation,***,their extensive applications were limited by their low catalytic activity ***,we have presented a composite nanozyme based on attapulgite(ATP)(Fe-ATP-MoS_(2)(FAM)),which exhibited enhanced POD-like activity(185.33 U·mg^(−1)),4.25 times higher than that of Fe-MoS_(2)(FM)(43.63 U·mg^(−1)).The density functional theory(DFT)calculations indicated that the addition of ATP increased the electron density of metal centers(Mo and Fe).More importantly,Michaelis–Menten kinetics revealed that the introduction of ATP significantly enhanced the binding affinities of substrates through the pores of ATP,forming a highly concentrated substrate microenvironment and thus promoting its POD-like ***,from molecular size and kinetic analysis,we proposed that the changes in substrate size before and after oxidation also significantly affected its Michaelis-constant(Km)***,we utilized FAM in the applications of highly effective antibacterial application and sensitive detection of glutathione(GSH).In conclusion,this work provides a novel approach for designing a highly efficient nanozyme based on natural mineral composites.

关键词： attapulgite peroxidase electron density affinity antibacterial