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江西建材 2024年第12期 382-384页

作者：孙梦张月张绪雯黑龙江科技大学建筑工程学院黑龙江哈尔滨150022

为了验证最佳配比下PU沥青混合料在寒区应用的优越性,文中利用ABAQUS软件,采用对比研究的方式,展开PU改性沥青混合料面层与普通沥青混合料面层的路面结构力学响应差异分析,结合寒区大温差特点设置了温度梯度变化,体现PU改性后具有减小... 详细信息

为了验证最佳配比下PU沥青混合料在寒区应用的优越性,文中利用ABAQUS软件,采用对比研究的方式,展开PU改性沥青混合料面层与普通沥青混合料面层的路面结构力学响应差异分析,结合寒区大温差特点设置了温度梯度变化,体现PU改性后具有减小应力应变受温度影响的作用。结果表明,整体抗压回弹模量得到了提升,其应力扩散效应也随之增强,从而使整体沥青路面结构的力学性能得到提升。

关键词：最佳配比 PU沥青混合料温度梯度

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甲午战败的国防文化反思

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军事交通学院学报 2017年第3期19卷 79-82页

作者：孙绪闻王璐颖南京政治学院上海校区上海200433 第二军医大学政治部上海200433

甲午战败虽有多方面原因,但根源是国防文化的衰败。为使军队铭记屈辱历史、汲取惨痛教训,更好地推进新形势下的国防文化建设,从落后的国防思想文化决定了清军未战先败、淡薄的国防观念文化导致了军事上的惨败、没落的国防经济文化引起... 详细信息

甲午战败虽有多方面原因,但根源是国防文化的衰败。为使军队铭记屈辱历史、汲取惨痛教训,更好地推进新形势下的国防文化建设,从落后的国防思想文化决定了清军未战先败、淡薄的国防观念文化导致了军事上的惨败、没落的国防经济文化引起了清末国防衰败等3个方面对甲午战败进行深刻的国防文化反思。

关键词：甲午战争国防文化国防建设

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糯玉米自交系籽粒淀粉理化特性的相关和聚类分析

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扬州大学学报（农业与生命科学版） 2021年第3期42卷 97-103页

作者：徐广海张成冉孙鹏赵延明江绪文孙晴晴张海艳青岛农业大学农学院/山东省旱作农业重点实验室山东青岛266109

以54个糯玉米自交系为材料,对其籽粒淀粉物质组成和理化特性进行相关和聚类分析。结果表明:供试材料淀粉理化特性在自交系间差异显著,淀粉理化特性与淀粉物质组成含量密切相关。淀粉糊化特性参数之间显著相关。蛋白质含量、脂肪含量、... 详细信息

以54个糯玉米自交系为材料,对其籽粒淀粉物质组成和理化特性进行相关和聚类分析。结果表明:供试材料淀粉理化特性在自交系间差异显著,淀粉理化特性与淀粉物质组成含量密切相关。淀粉糊化特性参数之间显著相关。蛋白质含量、脂肪含量、直链淀粉含量与膨胀势、峰值黏度、低谷黏度、崩解值、最终黏度呈显著负相关,与蓝值(蛋白质含量除外)、糊化温度呈显著正相关;直链淀粉含量与碘结合力呈极显著正相关,与回复值呈极显著负相关。根据糊化特性可将54个糯玉米自交系聚为3类,3类自交系的个数分别为29、17、8。各类之间的差异主要反映为其黏度值的大小,第Ⅰ类黏度值大,类内变异系数小;第Ⅲ类黏度值小,类内变异系数大;第Ⅱ类介于两者之间。因此,类群Ⅰ中的自交系材料具有黏度高、易糊化等优良特性且表现稳定,可作为骨干亲本用于糯玉米淀粉品质的改良。

关键词：糯玉米淀粉理化特性相关分析聚类分析

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Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidines as atypical protein kinase C inhibitors to control retinal vascular permeability and cytokine-induced edema

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BIOORGANIC & MEDICINAL CHEMISTRY 2020年第11期28卷 115480-115480页

作者： Liu, xuwen Wilson, Michael W. Liu, Kun Lee, Pil Yeomans, Larisa Hagen, Susan E. Lin, Cheng-Mao Wen, Bo sun, Duxin White, Andrew D. Showalter, Hollis D. Antonetti, David A. Univ Michigan Dept Ophthalmol & Visual Sci Ann Arbor MI 48105 USA Univ Michigan Dept Med Chem Ann Arbor MI 48105 USA Univ Michigan Vahlteich Med Chem Core Ann Arbor MI 48109 USA Univ Michigan Dept Pharmaceut Sci Ann Arbor MI 48109 USA Univ Michigan Dept Mol & Integrat Physiol Ann Arbor MI 48109 USA

Studies demonstrate that small molecule targeting of atypical protein kinase C (aPKC) may provide an effective means to control vascular permeability, prevent edema, and reduce inflammation providing novel and important alternatives to anti-VEGF therapies for certain blinding eye diseases. Based on a literature tricyclic thieno[2,3-d] pyrimidine lead (1), an ATP-competitive inhibitor of the aPKC iota (iota) and aPKC zeta (zeta) isoforms, we have synthesized a small series of compounds in 1-2 steps from a readily available chloro intermediate. A single pyridine congener was also made using 2D NMR to assign regiochemistry. Within the parent pyrimidine series, a range of potencies was observed against aPKC zeta whereas the pyridine congener was inactive. Selected compounds were also tested for their effect toward VEGF-induced permeability in BREC cells. The most potent of these (7l) was further assayed against the aPKC iota isoform and showed a favorable selectivity profile against a panel of 31 kinases, including kinases from the AGC superfamily, with a focus on PKC isoforms and kinases previously shown to affect permeability. Further testing of 7l in a luciferase assay in HEK293 cells showed an ability to prevent TNF-alpha induced NF kappa B activation while not having any effect on cell survival. Intravitreal administration of 7l to the eye yielded a complete reduction in permeability in a test to determine whether the compound could block VEGF- and TNF alpha-induced permeability across the retinal vasculature in a rat model. The compound in mice displayed good microsomal stability and in plasma moderate exposure (AUC and C-max), low clearance, a long half-life and high oral bioavailability. With IV dosing, higher levels were observed in the brain and eye relative to plasma, with highest levels in the eye by either IV or PO dosing. With a slow oral absorption profile, 7l accumulates in the eye to maintain a high concentration after dosing with higher levels than in

关键词： Blinding eye diseases atypical protein kinaseC (aPKC) Vascular permeability Vascular endothelial growth factor (VEGF) Tumor necrosis factor-alpha (TNF alpha) Homology model Thieno[2,3-d]pyrimidine inhibitors SAR

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Communication between the Ligand-Binding Pocket and the Activation Function-2 Domain of Androgen Receptor Revealed by Molecular Dynamics Simulations

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JOURNAL OF CHEMICAL INFORMATION AND MODELING 2019年第2期59卷 842-857页

作者： Jin, Ye Duan, Mojie Wang, xuwen Kong, Xiaotian Zhou, Wenfang sun, Huiyong Liu, Hui Li, Dan Yu, Huidong Li, Youyong Hou, Tingjun Soochow Univ Inst Funct Nano & Soft Mat FUNSOM Suzhou 215123 Jiangsu Peoples R China Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Zhejiang Peoples R China Zhejiang Univ State Key Lab CAD&CG Hangzhou 310058 Zhejiang Peoples R China Chinese Acad Sci Key Lab Magnet Resonance Biol Syst State Key Lab Magnet Resonance & Atom & Mol Phys Natl Ctr Magnet Resonance WuhanWuhan Inst Phys & Wuhan 430071 Peoples R China Rongene Pharma Co Ltd Shenzhen 518054 Guangdong Peoples R China

Androgen receptor (AR), as a member of the nuclear receptor (NR) superfamily, regulates the gene transcription in response to the sequential binding of diverse agonists and coactivators. Great progress has been made in studies on the pharmacology and structure of AR, but the atomic level mechanism of the bidirectional communications between the ligand-binding pocket (LBP) and the activation function-2 (AF2) region of AR remains poorly understood. Therefore, in this study, molecular dynamics (MD) simulations and free energy calculations were carried out to explore the interactions among water, agonist (DHT) or antagonist (HFT), AR, and coactivator (SRC3). Upon the binding of an agonist (DHT) or antagonist (HFT), the LBP structure would transform to the agonistic or antagonistic state, and the conformational changes of the LBP would regulate the structure of the AF2 surface. As a result, the binding of the androgen DHT could promote the recruitment of the coactivator SRC3 to the AF2, and on the contrary, the binding of the antagonist HFT would induce a perturbation to the shape of the AF2 and then weaken its accommodating capability of the coactivators with the LXXLL motif. The simulation results illustrated that the DHT-AR binding affinity was enhanced by the association of the coactivator SRC3, which would reduce the conformational fluctuation of the AR-LBD and expand the size of the AR LBP. On the other hand, the coactivator-to-HFT allosteric pathway, which involves the SRC3, helix 3 (H3), helix 4 (H4), the loop (L1-3) between helix 1 (H1) and H3, and HFT, was characterized. The HFT's skewness and different interactions between HFT and the LBP were observed in the SRC3-present AR The mutual communications between the AF2 surface and LBP, together with the processes involving the interplay of the ligand binding and coactivator recruitment events, would help in understanding the association of coactivators and rationally develop potent drugs to inhibit the activity o

关键词： Free energy Peptides and proteins Ligands Chemical structure Receptors

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A Micro-Environment Regulator for Filling the Clinical Treatment Gap after a Glioblastoma Operation

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ADVANCED HEALTHCARE MATERIALS 2022年第3期11卷 2101578-2101578页

作者： Zhang, Yiwen You, Haoyu Wang, Yaoben Chen, Qinjun Guo, Qin Chu, Yongchao Li, Chao Zhou, Wenxi Chen, Hongyi Liu, Peixin Wang, Yu Zhao, Zhenhao Zhou, Zheng Luo, Yifan Li, xuwen Zhang, Tongyu Song, Haolin Li, Chufeng Su, Boyu sun, Tao Bi, Yunke Yu, Lin Jiang, Chen Fudan Univ Sch Pharm Dept PharmaceutState Key Lab Med Neurobiol & MOE Inst Brain SciMinist EducKey Lab Smart Drug Del Shanghai 201203 Peoples R China Fudan Univ Dept Macromol Sci State Key Lab Mol Engn Polymers Shanghai 200438 Peoples R China Shanghai Jiao Tong Univ Sch Med Shanghai Gen Hosp Dept Neurosurg Shanghai 201203 Peoples R China

The rapid postoperative recurrence and short survival time of glioblastoma (GBM) patients necessitate immediate and effective postoperative treatment. Herein, an immediate and mild postoperative local treatment strategy is developed that regulates the postoperative microenvironment and delays GBM recurrence. Briefly, an injectable hydrogel system (imGEL) loaded with Zn(II)(2)-AMD3100 (AMD-Zn) and CpG oligonucleotide nanoparticles (CpG NPs) is injected into the operation cavity, with long-term function to block the recruitment of microglia/ macrophages and activate cytotoxic T cells. The finding indicated that the imGEL can regulate the immune microenvironment, inhibit GBM recurrence, and gain valuable time for subsequent adjuvant clinical chemotherapy.

关键词： drug delivery glioblastoma injectable hydrogels microenvironments post-operative therapy

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Biomimetic Dendrimer-Peptide Conjugates for Early Multi-Target Therapy of Alzheimer's Disease by Inflammatory Microenvironment Modulation

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ADVANCED MATERIALS 2021年第26期33卷 2100746-2100746页

作者： Liu, Peixin Zhang, Tongyu Chen, Qinjun Li, Chao Chu, Yongchao Guo, Qin Zhang, Yiwen Zhou, Wenxi Chen, Hongyi Zhou, Zheng Wang, Yu Zhao, Zhenhao Luo, Yifan Li, xuwen Song, Haolin Su, Boyu Li, Chufeng sun, Tao Jiang, Chen Fudan Univ Key Lab Smart Drug Delivery Minist Educ State Key Lab Med Neurobiol Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Dept Pharmaceut Sch Pharm Shanghai 201203 Peoples R China

Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on beta-amyloid (A beta) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD. Based on the crosstalk between inflammatory response and brain cells, a reactive oxygen species (ROS)-responsive dendrimer-peptide conjugate (APBP) is devised to target the AD microenvironment and inhibit inflammatory responses at an early stage. With the modification of the targeting peptide, this nanoconjugate can efficiently deliver peptides to the infected regions and restore the antioxidant ability of neurons by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway. Moreover, this multi-target strategy exhibits a synergistic function of ROS scavenging, promoting A beta phagocytosis, and normalizing the glial cell phenotype. As a result, the nanoconjugate can reduce ROS level, decrease A beta burden, alleviate glial cell activation, and eventually enhance cognitive functions in APPswe/PSEN1dE9 model mice. These results indicate that APBP can be a promising candidate for the multi-target treatment of AD.

关键词： Alzheimer&apos s disease antioxidant ability glial cell activation inflammatory responses multi‐ target treatments synergistic function

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An Algorithm for the Noninvasive and Personalized Measurement of Microvascular Blood Viscosity Using Physiological Parameters

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BIOMED RESEARCH INTERNATIONAL 2020年第0期2020卷 000-000页

作者： sun, Ge Yang, Lin Wang, Weiwei Zhang, Song Luo, Zhichang Wu, Guanghui Liu, Xiaohong Hao, Dongmei Yang, Yimin Li, xuwen Beijing Univ Technol Fac Environm & Life Sci Beijing 100124 Peoples R China Beijing Int Sci & Technol Cooperat Base Intellige Beijing 100124 Peoples R China Chinese Acad Med Sci Fuwai Hosp Beijing 100037 Peoples R China Capital Med Univ Beijing Inst Heart Lung & Blood Vessel Dis Beijing Anzhen Hosp Beijing 100029 Peoples R China Beijing Yes Med Devices Co Ltd Beijing 100152 Peoples R China

Blood viscosity is one of the important parameters to characterize hemorheological properties of the human body. Its real-time and dynamic measurement has important physiological significance for studying the development and prevention of chronic diseases. This study researched noninvasive and personalized measurement of microvascular blood viscosity. In the microcirculation capillary network blood flow model, combined with pulse wave parameters, multiple regression analysis was used to fit the simulated radius of personalized physiological blood vessels to calculate the microvascular blood viscosity. The fitted value related to the simulated radius of the physiological blood vessel had a high correlation with the corresponding theoretically derived value (correlation coefficient: 0.904,P <= 0.001). The calculated value of the microvascular blood viscosity had a certain correlation with the clinical whole blood viscosity at a low shear rate (correlation coefficient: 0.443,P<0.05). This algorithm could provide effective means for noninvasive and long-term individual monitoring and family health care.

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论我国国防文化的基本特征

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理论界 2016年第6期 79-87页

作者：孙绪闻南京政治学院上海校区

国防文化是战争实践和国防建设过程中的一种精神积淀和文化提炼,是我军政治工作的拓展和延伸,具有"以文为里以武为表"、"以谋为上以力为下"、"以民为源以军为主""以和为守以战为指"、"以... 详细信息

国防文化是战争实践和国防建设过程中的一种精神积淀和文化提炼,是我军政治工作的拓展和延伸,具有"以文为里以武为表"、"以谋为上以力为下"、"以民为源以军为主""以和为守以战为指"、"以防为本以攻为要"等基本特征,充分认识国防文化的特征,对于充分发挥国防文化的功能,指导、加强国防和军队建设有着重要作用。

关键词：国防文化尚武精神军事谋略国防建设攻势防御

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基于关键特征的船用柴油机机身工艺可靠性评价系统开发

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机床与液压 2021年第19期49卷 72-76,84页

作者：杨威斌景旭文肖志建周宏根赵晨华孙丽李国超江苏科技大学机械工程学院江苏镇江212003 广船国际有限公司广东广州510000 陕西柴油机重工有限公司陕西咸阳713100

船用柴油机机身加工工艺复杂,为实现对机身工艺可靠性的评估,开发基于关键特征的船用柴油机机身工艺可靠性评价系统。该系统实现了对机身加工工艺信息的管理、关键特征的筛选,进而实现了对船用柴油机机身工艺可靠性的评估,为快速评价加... 详细信息

船用柴油机机身加工工艺复杂,为实现对机身工艺可靠性的评估,开发基于关键特征的船用柴油机机身工艺可靠性评价系统。该系统实现了对机身加工工艺信息的管理、关键特征的筛选,进而实现了对船用柴油机机身工艺可靠性的评估,为快速评价加工策略的优劣提供了可视化操作平台和决策支持。研究结果为机身实际生产加工提供了参考。

关键词：加工工艺工艺可靠性评价系统关键特征数据库

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