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Identification of marine natural product Pretrichodermamide B as a STAT3 inhibitor for efficient anticancer therapy

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Marine Life Science & Technology 2023年第1期5卷 94-101页

作者： Rui Li Yue Zhou Xinxin Zhang lujia Yang Jieyu Liu Samantha M.Wightman Ling Lv Zhiqing Liu Chang-Yun Wang Chenyang Zhao School of Medicine and Pharmacy Institute of Evolution&Marine BiodiversityCollege of Food Science and EngineeringOcean University of ChinaQingdao266003China Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and TechnologyQingdao266237China Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOH44195USA

The Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)regulates the expression of various critical mediators of cancer and is considered as one of the central communication nodes in cell growth and *** natural products(MNP)represent great resources for discovery of bioactive lead compounds,especially anti-cancer *** the medium-throughput screening of our in-house MNP library,Pretrichodermamide B,an epidithiodiketopiperazine,was identified as a JAK/STAT3 signaling *** studies identified that Pretrichodermamide B directly binds to STAT3,preventing phosphorylation and thus inhibiting JAK/STAT3 ***,it suppressed cancer cell growth,in vitro,at low micromolar concentrations and demonstrated efficacy in vivo by decreasing tumor growth in a xenograft mouse *** addition,it was shown that Pretrichodermamide B was able to induce cell cycle arrest and promote cell *** study demonstrated that Pretrichodermamide B is a novel STAT3 inhibitor,which should be considered for further exploration as a promising anti-cancer therapy.

关键词： Pretrichodermamide B Signal transducer and activator of transcription 3(STAT3) Marine natural products Target protein In vivo anti-cancer efficacy

The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3567-3583页

作者： Chengdi Wang Qiuxiao Yu Tingting Song Zhoufeng Wang lujia Song Ying Yang Jun Shao Jingwei Li Yinyun Ni Ningning Chao Li Zhang Weimin Li Department of Respiratory and Critical Care Medicine Med-X Center for ManufacturingCenter of Precision MedicinePrecision Medicine Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalWest China Medical SchoolSichuan University610041 ChengduChina National Cancer Center National Clinical Research Center for CancerCancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical College518116ShenzhenChina

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer(NSCLC)***-cell RNA sequencing(scRNA-seq)techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC),the two major subtypes of ***,we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients,and drew a systematic immune cell transcriptome *** analyses of the distinct cellular compositions,differentilly expressed genes(DEGs),cell-cell interactions,pseudotime trajectory,transcriptomic factors and prognostic factors based on The Cancer Genome Atlas(TCGA),revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages(Mo)subtypes in the immune microenvironment heterogeneity between LUAD and *** dominant subtype of Mo was FABP4-Mp in LUAD and SPP1-Mo in ***,we identifieda novel lymphocyte-related Mo cluster,which we named SELENOP-Mo,and further established its antitumor role in both types,especially in *** comprehensive depiction of the immune heterogeneity and definition of Mp clusters could help design personalized treatment for lung cancer patients in clinical practice.

关键词： lung squamous adenocarcinoma

基于红外光谱的不同农作物秸秆磨木木质素差异表征

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农业工程学报 2018年第19期34卷 219-224页

作者：杨增玲梅佳琪曹聪纪冠亚韩鲁佳中国农业大学工学院

木质素是植物细胞壁中主要组分之一,其苯丙烷结构单元的单体结构和连接方式的复杂性直接影响木质素脱除和利用效果,了解不同农作物秸秆中木质素的差异,对提高秸秆的综合利用效率是非常必要的。该文选取代表性棉秆、玉米秸和小麦秆,分别... 详细信息

木质素是植物细胞壁中主要组分之一,其苯丙烷结构单元的单体结构和连接方式的复杂性直接影响木质素脱除和利用效果,了解不同农作物秸秆中木质素的差异,对提高秸秆的综合利用效率是非常必要的。该文选取代表性棉秆、玉米秸和小麦秆,分别提取磨木木质素,利用傅里叶变换中红外技术对棉秆、玉米秸和小麦秆三类秸秆磨木木质素进行红外表征,分析比较三类秸秆磨木木质素的差异,结果表明:1)三类秸秆磨木木质素G/S相对比值差别不大,并无明显规律;2)三类秸秆磨木木质素中,对羟基结构单元:玉米秸>小麦秆>>棉秆;愈创木基结构单元:棉秆>玉米秸>小麦秆;紫丁香基结构单元:玉米秸>小麦秆>棉秆;3)玉米秸和小麦秆磨木木质素相似度较高,而棉秆磨木木质素则更加接近于木本植物。

关键词：秸秆作物光谱分析磨木木质素红外光谱

Study on Processing Technology for Aconiti Kusnezoffii Radix by Bean Curd

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Medicinal Plant 2018年第4期9卷 65-67,72页

作者： Hongtao YANG lujia SHOU Zhiqiang CHEN Hangzhou Huadong Chinese Herbal Medicines Co. Ltd.

[Objectives] The aim was to explore the best parameters for processing Aconiti Kusnezoffii Radix by bean curd. [Methods] Orthogonal test( L_(16)(4~3)) was designed to investigate the optimal soaking time,decocting time and bean curd proportion for processing Aconiti Kusnezoffii Radix by bean curd. The contents of monoester alkaloids and diester-alkaloids were measured as the evaluation indexes. [Results]The contents of monoester alkaloids were 0. 11%,0. 07%,0. 062% and 0. 048% respectively under the four levels of soaking time,were0. 081%,0. 066%,0. 074% and 0. 067% respectively under the four levels of decocting time,and were 0. 070%,0. 072%,0. 080% and0. 073% respectively under the four levels of bean curd proportion. The content of diester-alkaloids was all below 0. 034%. The influence intensity of the three factors on the content of monoester alkaloids ranked as soaking time > decocting time > bean curd proportion. Under any of the above conditions,the content of diester-alkaloids was below the limit of Chinese Pharmacopoeia. The content of diester-alkaloids was reduced obviously with the increased use of bean curd. [Conclusions] The optimum processing conditions for Aconiti Kusnezoffii Radix were A_3B_3C_2,i. e.,soaking time of 6 d,decocting time of 5 h and bean curd proportion of 25%.

关键词： Aconiti Kusnezoffii Radix Prepared Aconiti Kusnezoffii Radix Aconitum kusnezoffii Process with bean curd Processing technology

Neural Network Model for Classifying the Economic Recession and Construction of Financial Stress Index

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国际计算机前沿大会会议论文集 2019年第2期 577-578页

作者： lujia Shen Tianyu Du Shouling Ji Northeastern University Bsoton MA 02120 USA Zhejiang Univerisity Hangzhou Zhejiang China

In this paper, a C5.0 decision tree and neural network models are proposed to classify recessions in the US with 12 common financial indices and new financial stress indices inferred from the neural network models are created. A detailed experiment is presented and demonstrates that the neural network models with proper regularization and dropout achieve 98% accuracy in the training set, 97% accuracy in validation set and 100% accuracy in test accuracy. The financial stress indices outperform other existing financial stress indices in many scenes and can accurately locate crisis events even the most recent 2018 US Bear Market. With these models and new indices, contraction can be detected before NBER’s announcement and action could be taken as early as the situation get worse.

关键词： Financial crisis Neural network Financial stress index

Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3916-3930页

作者： Zezhong Mou Yiling Chen Jinzhong Hu Yun Hu lujia Zou Xinan Chen Shenghua Liu Qiuping Yin Jian Gong Shuchen Li Shanhua Mao Chenyang Xu Haowen Jiang Department of Urology Huashan HospitalFudan UniversityShanghai 200040China Fudan Institute of Urology Fudan UniversityShanghai 200040China National Clinical Research Center for Aging and Medicine Fudan UniversityShanghai 200040China

Tumor relapse and metastasis are the major causes of mortality associated with urothelial *** the tumor microenvironment,negative regulatory molecules and various immune cell subtypes suppress antitumor *** inflammatory microenvironment,associated with neutrophils and neutrophil extracellular traps(NETs),promotes tumor ***,no drugs are currently available to specifically inhibit neutrophils and *** this study,we first demonstrated that icaritin(ICT),a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma,reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor ***,ICT binds to and inhibits the expression of PADI2 in neutrophils,thereby suppressing PADI2-mediated histone ***,ICT inhibits ROS generation,suppresses the MAPK signaling pathway,and inhibits NET-induced tumor ***,ICT inhibits tumoral PADI2-mediated histone citrullination,which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and *** downregulation of IL-6 expression,in turn,forms a regulatory feedback loop through the JAK2/STAT3/IL-6 *** a retrospective study of clinical samples,we found a correlation between neutrophils,NETs,UCa prognosis,and immune *** ICT with immune checkpoint inhibitors may have synergistic *** summary,our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

关键词： Icaritin Neutrophil Neutrophil extracellular trap PADI2 Urothelial cancer

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鱼粉中氨基酸近红外光谱定量分析

农业机械学报 2007年第5期38卷 114-117页

作者：牛智有韩鲁佳华中农业大学工程技术学院中国农业大学工学院

收集了145个鱼粉样本,应用偏最小二乘(PLS)方法,建立了鱼粉中17种氨基酸和总氨基酸NIRS定标模型。天冬氨酸、蛋氨酸、赖氨酸、苏氨酸、谷氨酸、甘氨酸、丙氨酸、缬氨酸、异亮氨酸、亮氨酸、苯丙氨酸、精氨酸、脯氨酸和总氨基酸的化学分... 详细信息

收集了145个鱼粉样本,应用偏最小二乘(PLS)方法,建立了鱼粉中17种氨基酸和总氨基酸NIRS定标模型。天冬氨酸、蛋氨酸、赖氨酸、苏氨酸、谷氨酸、甘氨酸、丙氨酸、缬氨酸、异亮氨酸、亮氨酸、苯丙氨酸、精氨酸、脯氨酸和总氨基酸的化学分析值与NIRS预测值的决定系数R2都达到0.87以上,相对标准差均小于10%,相对分析误差均大于3;酪氨酸的决定系数R2为0.8678,相对标准差为8.65%,相对分析误差为2.77;组氨酸、丝氨酸和半胱氨酸的决定系数R2分别为0.9005、0.7436和0.3541,相对标准差分别为14.19%、17.85%和33.85%,相对分析误差分别为2.96、1.98和1.04。结果表明,利用近红外光谱分析技术能够较准确地检测鱼粉中14种氨基酸;酪氨酸只能进行粗略估测;组氨酸、丝氨酸和半胱氨酸难于进行实际检测。

关键词：鱼粉氨基酸近红外反射光谱偏最小二乘定量分析

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饲料中肉骨粉含量的近红外反射光谱检测方法

农业工程学报 2008年第4期24卷 271-274页

作者：牛智有韩鲁佳华中农业大学工程技术学院武汉430070 中国农业大学工学院北京100083

收集28份鸡饲料,31份猪饲料,25份牛饲料和肉骨粉7份,在饲料中掺入不同比例(0.5%～6.0%)的肉骨粉,制成分析样本。采用偏最小二乘(PLS)法,分别对光谱进行散射校正、平滑、一阶导数和二阶导数预处理,建立了鸡饲料、猪饲料和牛饲料中肉骨粉... 详细信息

收集28份鸡饲料,31份猪饲料,25份牛饲料和肉骨粉7份,在饲料中掺入不同比例(0.5%～6.0%)的肉骨粉,制成分析样本。采用偏最小二乘(PLS)法,分别对光谱进行散射校正、平滑、一阶导数和二阶导数预处理,建立了鸡饲料、猪饲料和牛饲料中肉骨粉含量的近红外定量分析模型。利用验证集样本对定标模型进行了检验,鸡饲料、猪饲料和牛饲料中肉骨粉含量的真值与预测值之间的决定系数分别为0.9694、0.9846和0.9788;标准差分别为0.279、0.252和0.287;相对分析误差分别为5.663、6.865和5.889。结果表明,利用近红外光谱法测定饲料中的肉骨粉含量具有较高的预测精度。

关键词：近红外反射光谱饲料肉骨粉检测

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Persistent increase and improved survival of stage I lung cancer based on a large-scale real-world sample of 26,226 cases

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Chinese Medical Journal 2023年第16期136卷 1937-1948页

作者： Chengdi Wang Jun Shao lujia Song Pengwei Ren Dan Liu Weimin Li Department of Pulmonary and Critical Care Medicine Med-X Center for ManufacturingFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengduSichuan 610041China

Background:Lung cancer prevails and induces high mortality around the *** study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer,and provided survival information within stage I ***:Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information,molecular testing results,and follow-up *** in clinical characteristics were evaluated usingχ^(2)*** survival(OS)was calculated through the Kaplan-Meier ***:A total of 26,226 eligible lung cancer patients were included,among whom 62.55%were male and 52.89%were ***-smokers and elderly patients took increasingly larger proportions in the whole patient *** proportion of adenocarcinoma increased from 51.63%to 71.80%,while that of squamous carcinoma decreased from 28.43%to 17.60%.Gene mutations including EGFR(52.14%),KRAS(12.14%),and ALK(8.12%)were ***,younger,non-smoking,adenocarcinoma patients and those with mutated EGFR had better survival ***,this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the *** with stage I lung cancer,accounted for an increasingly considerable proportion,increasing from 15.28%to 40.25%,coinciding with the surgery rate increasing from 38.14%to 54.25%.Overall,period survival analyses found that 42.69%of patients survived 5 years,and stage I patients had a 5-year OS of 84.20%.Compared with that in 2009-2013,the prognosis of stage I patients in 2014-2018 was dramatically better,with 5-year OS increasing from 73.26%to 87.68%.Regarding the specific survival benefits among stage I patients,the 5-year survival rates were 95.28%,93.25%,82.08%,and 74.50%for stage IA1,IA2,IA3,and IB,respectively,far more promising than previous ***:Crucial clinical and pa

关键词： Lung neoplasms Clinicopathological characteristics TNM staging Pathological subtypes Survival analysis

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