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Size and Charge Dual-Switchable Nanoparticles for Achieving Chemosensitization and Immune Infiltration against Pancreatic Ductal Adenocarcinoma

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ADVANCED FUNCTIONAL MATERIALS 2025年第1期35卷

作者： Song, Haolin Chen, Hongyi Chen, Qinjun Fan, Hongrui Li, Chufeng wang, Yu Zhang, Shilin Li, xuwen Su, Boyu Sun, Tao Jiang, Chen Fudan Univ Sch Pharm Dept Pharmaceut Key Lab Smart Drug DeliveryMinist EducState Key Shanghai 201203 Peoples R China MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China Fujian Med Univ Affiliated Hosp 1 Natl Reg Med Ctr Dept Digest Dis Binhai Campus Fuzhou 350212 Peoples R China

Pancreatic ductal adenocarcinoma (PDAC), one of the most challenging cancers, is uniquely characterized by a biological barrier composed of multiple components in the extracellular matrix, preventing penetration of chemotherapeutic agents and hindering clinical drug treatment. Collagen I arrangement is critical. In this study, gemcitabine is chosen as the chemotherapeutic agent and dasatinib as the collagen-I-disrupting agent. When collagen I arrangement is disrupted, not only the chemotherapeutic drug enters the tumor area better, but the infiltration of CD8+ T cells into the tumor also increases. Therefore, a hypoxia-responsive linker-crosslinked polymer, DGD/L@GBI, is designed, which can be simultaneously loaded with two therapeutic agents, gemcitabine and dasatinib. The polymer is encapsulated by nucleic acid aptamers that target the PDAC stromal microenvironment and shield the surface. The aptamer is removed upon arrival at the PDAC hypoxic microenvironment, exposing the positively charged core to achieve charge reversal. Particle size transformation is achieved using linkers that respond to a hypoxic microenvironment. Increased intratumoral penetration is achieved using the dual transformation capabilities of the formulation. Pairing these two agents can result in a powerful efficacy in chemotherapy sensitization and immune infiltration.

关键词： charge reversal chemosensitization immune infiltration pancreatic ductal adenocarcinoma size reduction

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Structural brain characteristics and gene co-expression analysis: A study with outcome label from normal cognition to mild cognitive impairment

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NEUROBIOLOGY OF LEARNING AND MEMORY 2022年第0期191卷 000-000页

作者： Cai, Suping Yang, Fan wang, xuwen Wu, Sijia Huang, Liyu Xidian Univ Sch Life Sci & Technol Xian 710071 Shaanxi Peoples R China

Background: Longitudinal studies reported that some elderly people with normal cognition (NC) converted to mild cognitive impairment (MCI), and some remained normal state (NC_S). The underlying factor for this difference conversion of NC is worthy of exploration Methods: Eighty-three NC participants were tracked for eight years. Thirty participants transitioned from NC to MCI (NC_MCI). The remaining 53 participants retained an NC_S. The structural brain features and genetic expression of the 83 NC participants were obtained. We applied weighted gene co-expression network analysis (WGCNA) to inquire into the co-expression network of those. Mediator effect analysis of regulatory roles was conducted to inquire into the associations between brain measures, expression values, and clinical scores. Results: The main results are: 1) 20 brain features and 740 gene expression had significant differences between the two groups, 2) one module including 187 genes had the most correlation with cortical thickness of left superior temporal sulcus (***), 3) NFKBIA and RARA genes were the top two genes that made the greatest contribution to *** thickness, and 4) mediating effect was found between the *** thickness, the NFKBIA and RARA expression levels, and clinical scores. Conclusion: Our results provide a theoretical foundation based on gene expression and brain imaging for the factors of NC with different outcomes.

关键词： Conversion WGCNA analysis T1-weighted MRI images NFKBIA and RARA genetic expression Mediator effect

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Study on Mechanical Behavior of Masonry Wall in School Building Reinforced by CFRP

Study on Mechanical Behavior of Masonry Wall in School Build...

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2013 International Conference on Materials Engineering and Mechanical Automation(MEMA 2013)

作者： Hong Lin Zhao Yang xuwen wang Xiang Ke Design and research institute Wuhan University of Technology Institute of Urban Construction Wuhan University of Science and Technology

CFRP is a new kind of building materials popularly used in structure *** order to study the reinforcement technique for masonry walls of school buildings,the walls with window opening strengthened by CFRP were studied in the *** on the experiment result,the finite element simulation and theoretical calculation analysis were done to study the mechanical behavior and shear capacity of the wall with window opening reinforced by *** CFRP pasted at the corner of window opening were proved to be effectively in improving shear capacity of the walls,and simple calculation formulas of shear capacity were provided in the paper,which proved to be accurate.

关键词： CFRP Masonry structure Mechanical behavior Shear capacity

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Development and Validation of a Screening Tool for Generalized Anxiety and Major Depressive Disorder in Patients with Chronic Obstructive Pulmonary Disease

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LUNG 2025年第1期203卷 1-12页

作者： Liu, Meishan Yang, xuwen wang, Dong Fang, Jiexin Li, Boyu An, Li Chang, Yuhan Liu, Haiman Hu, Yongdong Huang, Kewu Capital Med Univ Beijing Inst Resp Med Dept Resp & Crit Care Med 8Gongti South Rd Beijing 100020 Peoples R China Capital Med Univ Beijing Chao Yang Hosp 8Gongti South Rd Beijing 100020 Peoples R China Capital Med Univ Beijing Chao Yang Hosp Dept Clin Psychol 8Gongti South Rd Beijing 100020 Peoples R China Capital Med Univ Beijing Chao Yang Hosp Dept Pharm Beijing Peoples R China

PurposeAnxiety and depression are often underdiagnosed in patients with chronic obstructive pulmonary disease (COPD). This study aimed to develop and validate a screening tool for anxiety and depression in COPD *** COPD patients were consecutively recruited from November 2021 to October 2023 and underwent a psychiatric interview to diagnose generalized anxiety disorder (GAD) and/or major depressive disorder (MDD) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Patients were split into training and validation sets according to their recruitment time. We assessed known risk factors and used core items from the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) to develop a prediction nomogram. Multivariable logistic regression with least absolute shrinkage and selection operator (LASSO) were used to construct the *** the enrolled COPD patients (n = 329), 58 (25.6%) in the training cohort and 33 (32.4%) in the validation cohort were diagnosed with GAD and/or MDD. Three variables were identified in the prediction nomogram: COPD Assessment Test score and two core items from PHQ-ADS. The under the curve (AUC) value for the nomogram was 0.826 (95% CI: 0.755-0.897) and 0.855 (95% CI: 0.767-0.942) in the training and validation cohorts, respectively. The calibration curve was close to the diagonal. The discriminatory power of the screening nomogram was comparable to that of PHQ-ADS (AUC: 0.826 vs. 0.831, P = 0.832).ConclusionThe new screening tool for GAD and MDD in COPD patients is concise and valid, with discriminatory power comparable to existing anxiety/depression screening questionnaires.

关键词： Chronic obstructive pulmonary disease Anxiety Depression Screening Nomogram

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Structure-Based Drug Design and Identification of H₂O-Soluble and Low Toxic Hexacyclic Camptothecin Derivatives with Improved Efficacy in Cancer and Lethal Inflammation Models in Vivo

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JOURNAL OF MEDICINAL CHEMISTRY 2018年第19期61卷 8613-8624页

作者： Pang, Peichen Chen, Jiean Li, Xijian Li, Miyang Yu, Huidong Zhao, Jean J. Ni, Jing wang, xuwen Sun, Huiyong Tian, Sheng Zhu, Feng Liu, Feng Huang, Yong Hou, Tingjun Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Zhejiang Peoples R China Zhejiang Univ State Key Lab CAD&CG Hangzhou 310058 Zhejiang Peoples R China Peking Univ State Key Lab Chem Oncogen Key Lab Chem Genom Shenzhen Grad Sch Shenzhen 518055 Guangdong Peoples R China Rongene Pharma Co Ltd Guangzhou 510663 Guandong Peoples R China Dana Farber Canc Inst Dept Canc Biol Boston MA 02215 USA Harvard Med Sch Dept Biol Chem & Mol Pharmacol Boston MA 02215 USA Soochow Univ Coll Pharmaceut Sci Suzhou 215123 Jiangsu Peoples R China

Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I (Topo I)/DNA cleavable complex. However, the poor aqueous solubility, intrinsic instability, and severe toxicity of CPTs have limited their clinical applications. Herein, we report the design and synthesis of H2O-soluble and orally bioavailable hexacyclic CPT derivatives. By analysis of a virtual chemical library and cytotoxicity screening in vitro, 9 and 11 were identified as potential prodrugs and chosen for further characterization in vivo. Both compounds exhibited remarkable anticancer and anti-inflammation efficacies in animals and improved drug-like profiles.

关键词： Mixtures Rodent models Solubility Genetics Toxicity

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A RETRIEVAL MODEL FOR QUESTION IN COMMUNITY QUESTION ANSWERING SYSTEM

A RETRIEVAL MODEL FOR QUESTION IN COMMUNITY QUESTION ANSWERI...

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2012 IEEE 2nd International Conference on Cloud Computing and Intelligence Systems

作者： Yueping Sun Xiaojie wang Song Liu Caixia Yuan xuwen wang Center for Intelligence Science and Technology Research Beijing University of Posts and Telecommunications

Studies of Community-based question and answer services (cQA) have grown to be one of the emerging trends in Web information services. And one of the main tasks is to retrieve similar questions. To identify the fact that some questions with different expressions though may indeed have the same, or very similar, meaning, the similar questions are defined in syntactic, semantic and pragmatic aspects according to user retrieval intention. Five models including Language Model, Translation-based Language Model, Parser-based model, LDA and WordNet source-based model are selected as baselines. Integrated models which linearly combine WordNet, Stanford Parser and Language Model and further weighted by syntactic feature are proposed to integrate features of the three aspects. Experiment results show that our integrated models perform better than the basic models, especially when the linear combination of the WordNet model and the Stanford Parser model is weighted by syntactic information with proper noun phrases as representative. The integrated models are further verified by logistic analysis.

关键词： Community question answering system WordNet Language model Stanford parser Proper noun phrase

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利用粗糙集和支持向量机的银行借贷风险预测模型

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成都理工大学学报（自然科学版） 2022年第2期49卷 249-256页

作者：吴尚智王旭文王志宁任艺璇西北师范大学计算机科学与工程学院兰州730070

将粗糙集和支持向量机相结合,提出利用粗糙集和支持向量机的银行借贷风险预测模型,提高银行个人借贷风险预测精度,为银行判断是否同意借贷提供参考和依据。该模型首先将银行样本数据形成初始决策表,对其进行数据预处理;然后用属性相似... 详细信息

将粗糙集和支持向量机相结合,提出利用粗糙集和支持向量机的银行借贷风险预测模型,提高银行个人借贷风险预测精度,为银行判断是否同意借贷提供参考和依据。该模型首先将银行样本数据形成初始决策表,对其进行数据预处理;然后用属性相似度的属性约简算法对决策表进行属性约简,去除冗余属性,获得高效的决策规则;最后将约简后的最小属性作为4种不同核函数的支持向量机学习样本,构建预测模型且进行预测评价对比分析。实验结果表明,使用相同训练样本,高斯核函数的支持向量机预测模型的准确率最高且为93%,说明该预测模型具有较高的精度。通过实验分析,构建预测模型有效地预测了银行借贷风险,且为银行借贷管理提供辅助决策。

关键词：粗糙集属性约简支持向量机核函数预测模型

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Association between structural brain features and gene expression by weighted gene co-expression network analysis in conversion from MCI to AD

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BEHAVIOURAL BRAIN RESEARCH 2021年第0期410卷 113330-113330页

作者： wang, xuwen Huang, Kexin Yang, Fan Chen, Dihun Cai, Suping Huang, Liyu Xidian Univ Sch Life Sci & Technol Xian 710071 Shaanxi Peoples R China

Alzheimer's disease (AD) is a neurodegenerative disease. Mild cognitive impairment (MCI) represents a state of cognitive function between normal cognition and dementia. Longitudinal studies showed that some MCI patients remained in a state of MCI, and some developed AD. The reason for these different conversions from MCI remains to be investigated. 180 MCI participants were followed for eight years. 143 MCI patients maintained the MCI state (MCI_S), and the remaining thirty-seven MCI patients were re-evaluated as having AD (MCI_AD). We obtained 1,036 structural brain characteristics and 15,481 gene expression values from the 180 MCI participants and applied weighted gene co-expression network analysis (WGCNA) to explore the relationship between structural brain features and gene expression. Regulating mediator effect analysis was employed to explore the relationships among gene expression, brain region measurements and clinical phenotypes. We found that 60 genes from the MCI_S group and 18 genes from the MCI_AD group respectively had the most significant correlations with left paracentral lobule and sulcus (***) and right subparietal sulcus (***) thickness;CTCF, UQCR11 and WDR5B were the mutual genes between the two groups. The expression of CTCF gene and clinical score are completely mediated by *** thickness, and the UQCR11 and WDR5B gene expression levels significantly regulate the mediating effect pathway. In conclusion, the factors affecting the different conversions from MCI are closely related to *** thickness and the CTCF, UQCR11 and WDR5B gene expression levels. Our results add a theoretical foundation of imaging genetics for conversion from MCI to AD.

关键词： Weighted gene co-expression network analysis Structural magnetic resonance imaging CTCF UQCR11 and WDR5B genetic expression Regulatory mediator effect analysis Conversion

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Discovery of a Novel Androgen Receptor Antagonist Manifesting Evidence to Disrupt the Dimerization of the Ligand-Binding Domain via Attenuating the Hydrogen-Bonding Network Between the Two Monomers

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JOURNAL OF MEDICINAL CHEMISTRY 2021年第23期64卷 17221-17238页

作者： Fu, Weitao Zhang, Minkui Liao, Jianing Tang, Qing Lei, Yixuan Gong, Zhou Shan, Luhu Duan, Mojie Chai, Xin Pang, Jinping Tang, Chun wang, xuwen Xu, Xiaohong Li, Dan Sheng, Rong Hou, Tingjun Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Zhejiang Peoples R China Chinese Acad Sci Innovat Acad Precis Measurement Sci & Technol Natl Ctr Magnet Resonance WuhanState Key Lab Mag Wuhan Inst Phys & MathCAS Key Lab Magnet Resonan Wuhan 430071 Hubei Peoples R China Univ Chinese Acad Sci Zhejiang Canc Hosp Inst Canc Res & Basic Med Sci Canc HospChinese Acad Sci Hangzhou 310022 Zhejiang Peoples R China Chinese Acad Sci Natl Ctr Magnet Resonance Wuhan Wuhan Inst Phys & Math Key Lab Magnet Resonance Biol SystState Key Lab Wuhan 430071 Hubei Peoples R China Peking Univ Coll Chem & Mol Engn Beijing Natl Lab Mol Sci Beijing 100871 Peoples R China Peking Univ Peking Tsinghua Ctr Life Sci Beijing 100871 Peoples R China

Androgen receptor (AR) has proved to be a vital drug target for treating prostate cancer. Here, we reported the discovery of a novel AR antagonist 92 targeting the AR ligand-binding pocket, but distinct from the marketed drug enzalutamide (Enz), 92 demonstrated inhibition on the AR ligand-binding domain (LBD) dimerization, which is a novel mechanism reported for the first time. First, a novel hit (26, IC50 = 5.57 mu M) was identified through virtual screening based on a theoretical AR LBD dimer bound with the Enz model. Then, guided by molecular modeling, 92 was discovered with 32.7-fold improved AR antagonistic activity (IC50 = 0.17 mu M). Besides showing high bioactivity and safety, 92 can inhibit AR nuclear translocation. Furthermore, 92 inhibited the formation of the AR LBD dimer, possibly through attenuating the hydrogen-bonding network between the two monomers. This interesting finding would pave the way for the discovery of a new class of AR antagonists.

关键词： Antagonists Monomers Oligomers Assays Dimerization

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Development of an Interactive Medical Knowledge Graph Based Tool Set

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Procedia Computer Science 2023年 221卷 578-584页

作者： Xiaowei Xu xuwen wang Meng Wu Hetong Ma Liu Shen Jiao Li Institute of Medical Information & Library Chinese Academy of Medical Sciences& Peking Union Medical College Beijing 100020 China Key Laboratory of Medical Information Intelligent Technology Chinese Academy of Medical Sciences Beijing 100020 China

The field of clinical research has reached a turning point in terms of the range and diversity of available data and their potential to improve human health and well-being. However, due to discipline-specific variances in terminology and representation, the data is often compartmentalized, disorganized, and inaccessible to a broad audience. In response to these challenges, we designed and evaluated a pilot knowledge graph-based MedKaaS tool capable of integrating existing clinical datasets and translating those data into insights intended to augment human reasoning and accelerate scientific research. In this paper, we present the architecture and performance of our system, which has been applied to several real-world use cases in collaboration with subject-matter specialists. The MedKaaS Tools are actively developed, with regular updates to performance and features. Our future plans include developing a more user-friendly interface and expanding the visualization capabilities for knowledge exploration.

关键词： knowledge graph visualization application programming interface biomedical data

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