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Acta Pharmaceutica Sinica B 2022年第7期12卷 3103-3112页

作者： Xu-Nian wu Qian Zhou Ya-Dan Huang Xi Xie Zhe Li yinuo wu Hai-Bin Luo School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou510006China Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute School of Pharmaceutical SciencesHainan UniversityHaikou 570228China

Our previous study demonstrated that phosphodiesterase 8(PDE8)could work as a potential target for vascular dementia(Va D)using a chemical probe ***,compound 3a is a chiral compound which was obtained by chiral resolution on HPLC,restricting its usage in ***,a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 *** 15 exhibited potent inhibitory activity against PDE8A(IC_(50)=11 nmol/L),high selectivity over other PDEs,and remarkable drug-like properties(worthy to mention is that its bioavailability was up to 100%).Oral administration of 15 significantly improved the c AMP level of the right brain and exhibited dosedependent effects on cognitive improvement in a Va D mouse ***,the X-ray crystal structure of the PDE8A—15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shapedπ—πinteractions with Phe785 as well as a unique H-bond network,which have never been observed in other PDE-inhibitor complex before,providing new strategies for the further rational design of novel selective inhibitors against PDE8.

关键词： Phosphodiesterase 8(PDE8) Vascular dementia Structure-based drug design MM-GB/SA Free energy prediction Structure—activity relationship Binding potencies

基于PBL教学法的医学专业“基础化学”教学设计——以“溶液的渗透压”为例

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大学化学 2024年第3期39卷 149-157页

作者：吴一诺叶建涛周勰钱宇郭磊中山大学药学院广州510000

“基础化学”是医学专业本科生的必修课程,将为学生后续学习医学专业课程及工作奠定基础。学生无法意识到医学与化学的联系是学生学习兴趣不高的重要原因。为提升学生的学习积极性,本教学团队基于PBL教学法进行教学设计。以溶液的渗透... 详细信息

“基础化学”是医学专业本科生的必修课程,将为学生后续学习医学专业课程及工作奠定基础。学生无法意识到医学与化学的联系是学生学习兴趣不高的重要原因。为提升学生的学习积极性,本教学团队基于PBL教学法进行教学设计。以溶液的渗透压教学为例,通过引入多个与生活或医学密切相关的问题,有效激发学生学习兴趣,使学生带着问题去学习知识,提升了学生独立思考、举一反三、融会贯通的能力。多个思政元素的有效融入,有助于培养学生的爱国情怀、民族自豪感以及良好的医德医风。

关键词：基础化学问题导向教学法课程思政

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Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia:Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1180-1191页

作者： Qian Zhou Meiling Le Yiyi Yang Wenjuan Wang Yuqi Huang Quan Wang Yijing Tian Meiyan Jiang Yong Rao Hai-Bin Luo yinuo wu School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute School of Pharmaceutical SciencesHainan UniversityHaikou 570228China Song Li’Academician Workstation of Hainan University(School of Pharmaceutical Sciences) Sanya 572000China

Vascular dementia(VaD)is the second commonest type of dementia which lacks of efficient treatments *** as a prominent pathological feature of VaD,is highly involved in the development of *** order to verify the therapeutic potential of PDE1 inhibitors against VaD,the anti-neuroinflammation,memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor ***,the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically ***,to optimize the drug-like properties of 4a,especially for metabolic stability,15 derivatives were designed and *** a result,candidate 5f,with a potent IC50 value of 4.5 nmol/L against PDE1C,high selectivity over PDEs,and remarkable metabolic stability,efficiently ameliorated neuron degeneration,cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB *** results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

关键词： Vascular dementia Phosphodiesterase 1(PDE1) Neuroinflammation Structural-based drug design cAMP/CREB axis

Formation of a Hydrothermal Kaolinite Deposit from Rhyolitic Tuff in Jiangxi, China

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Journal of Earth Science 2014年第3期25卷 495-505页

作者： Ye Yuan Guanghai Shi Mengchu Yang yinuo wu Zhaochong Zhang Anjie Huang Jiajing Zhang State Key Laboratory of Geological Processes and Mineral Resources China University of Geosciences Geological Survey of Jiangxi Province Northeast Geological department of Jiangxi Geological Exploration Bureau

The Longmen kaolinite deposit is one of the largest hydrothermal clay deposits of Ganxi volcanic basin（northern wuyi Mountain area, China）. The pristine host rocks are rhyolitic crystal-vitric tuff and minor lapilli tuff from the Late Jurassic Ehuling Formation. The ore consists of kaolin-group minerals（kaolinite, dickite）, pyrophyllite with minor quartz, sericite, pyrite, etc.. From the host rocks to the transition zones（altered rocks） then to the vein ores, contents of SiO2 and TFe2O3 decrease, whereas Al2O3 and LOI increase, consistent with the contents increase of kaolin minerals and pyrophyllite in the samples. The total REE abundances of the ores are much lower than that of the host and altered rocks, Rb, Nb, Nd, Zr, Ti and Y are significantly depleted. Apparent zoning features of bulk geochemistry and mineral component reflect that the kaolinite deposit occurred at the expense of the host rock by ascending hydrothermal fluids with distinct removal of SiO2, TFe2O3, Na2O, K2O. According to the mineral assemblage, the formation temperature of this deposit falls within the range of 270–350 ℃. With regard to the industrial applications, the kaolinized ores are suitable for use in ceramics and gemologic materials crafted for seal stones. Moreover, in mineralogical terms, this deposit is also proved to be an excellent example for studying channeled hydrothermal alterations of rhyolitic tuff.

关键词： China geochemistry hydrothermal alteration Jiangxi kaolinite pyrophyllite.

Structure-based design,synthesis,and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors

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Acta Pharmaceutica Sinica B 2018年第4期8卷 615-628页

作者： Xu-Nian wu Ya-Dan Huang Jin-Xuan Li Yan-Fa Yu Qian Zhou Chen Zhang yinuo wu Hai-Bin Luo School of Pharmaceutical Sciences Sun Yat-sen University Collaborative Innovation Center of High Performance Computing National University of Defense Technology

The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPARγ agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC_(50) values 5n mol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma *** 11a, the most effective one, gave the IC_(50) of 1.1 nmol/L towards PDE9, which is significantly better than the reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding patterns and binding free energy of the designed compounds with PDE9 may explain the structure–activity relationships and provide evidence for further structural modifications.

关键词： PDE9 inhibitors Alzheimer’s disease Type 2 diabetes mellitus Rosiglitazone Molecular docking Dynamics simulation

Discovery of highly selective and orally available benzimidazole-based phosphodiesterase 10 inhibitors with improved solubility and pharmacokinetic properties for treatment of pulmonary arterial hypertension

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2339-2347页

作者： Yuncong Yangy Sirui Zhangy Qian Zhouy Chen Zhang Yuqi Gao Hao Wang Zhe Li Deyan wu yinuo wu Yi-You Huang Lei Guo Hai-Bin Luo School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China

Optimization efforts were devoted to discover novel PDE10 A inhibitors in order to improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension(PAH)starting from the previously synthesized inhibitor *** a result,a potent and highly selective PDE10 A inhibitor,14·3 HC1(half maximal inhibitory concentration,IC50=2.8 nmol/L and>3500-fold selectivity)exhibiting desirable solubility and metabolic stability with a remarkable bioavailability of50%was identified with the aid of efficient methods of binding free energy *** PAH studies showed that the improvement offered by 14·3 HCl[2.5 mg/kg,oral administration(p.o.)]was comparable to tadalafil(5.0 mg/kg,p.o.),verifying the feasibility of PDE10 A inhibitors for the antiPAH *** crystal structure of the PDE10 A-14 complex illustrates their binding pattern,which provided a guideline for rational design of highly selective PDE10 A inhibitors.

关键词： Phosphodiesterase 10A Inhibitor Benzimidazole derivatives Crystal structure Metabolic stability Bioavailability Pulmonary arterial hypertension

档案法律融入数据法律体系的内在逻辑、问题与路径

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档案学研究 2022年第3期 28-35页

作者：王玉珏吴一诺武汉大学信息管理学院武汉430072

档案法律应融入整个数据法律体系,其内在逻辑在于“数据”与“档案”的密切关系,即“数据态”是档案的存在形态之一,档案是需要长久保存的数据,对国家和社会具有保存价值的数据需要归档。然而,当前档案法律在数据长期保存中的角色有待明... 详细信息

档案法律应融入整个数据法律体系,其内在逻辑在于“数据”与“档案”的密切关系,即“数据态”是档案的存在形态之一,档案是需要长久保存的数据,对国家和社会具有保存价值的数据需要归档。然而,当前档案法律在数据长期保存中的角色有待明确,数据法律对档案工作造成挤压,档案法律对数据归档的解释力不足,为公共利益的存档与个人数据权益存在矛盾。为此,应该重塑“档案”认知和“归档”思维,构建数据协同治理机制,促进档案法律和数据法律下位法的协调。

关键词：数据法律档案法律长期保存数据治理

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高校日语教学融入中国传统文化通识教育刍论

成才之路 2022年第23期 113-116页

作者：吴以诺三江学院外国语学院江苏南京210000

在经济全球化的背景下,加强不同文化之间的交流沟通是时代发展的需要。这其中,日语对于中日两国之间的经贸往来、文化交流具有积极作用。而将中国传统文化通识教育融入高校日语教学中,有利于提高国家文化软实力,有利于促进不同文化之间... 详细信息

在经济全球化的背景下,加强不同文化之间的交流沟通是时代发展的需要。这其中,日语对于中日两国之间的经贸往来、文化交流具有积极作用。而将中国传统文化通识教育融入高校日语教学中,有利于提高国家文化软实力,有利于促进不同文化之间的交沆沟通,有利于提高学生的文化素养。文章在分析中国传统文化通识教育在日语教学中融入情况的基础上,结合中国传统文化通识教育融入日语教学的必要性,提出具体融合途径,以期培养出更多具有跨文化交际能力的高级日语人才。

关键词：日语教学中国传统文化通识教育融入

“心即理”导向下的国土空间规划理论认知和路径探索

同方期刊数据库博看期刊评论

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浙江大学学报（人文社会科学版） 2024年第4期54卷 70-85页

作者：邹依诺吴次芳谷玮浙江大学公共管理学院浙江杭州310058

“心即理”强调主体精神对宇宙万物的影响,更加符合生态文明时代的国土空间规划价值取向。“心即理”空间由精神空间、社会空间和物质空间组成,其中精神空间是“心即理”导向下国土空间规划重点营造的对象。此外,精神变量与客观福祉共... 详细信息

“心即理”强调主体精神对宇宙万物的影响,更加符合生态文明时代的国土空间规划价值取向。“心即理”空间由精神空间、社会空间和物质空间组成,其中精神空间是“心即理”导向下国土空间规划重点营造的对象。此外,精神变量与客观福祉共同构成了连续的幸福光谱,幸福光谱是构造诗意栖居环境的核心要素。精神空间由情感空间、快乐空间与诗居空间共同组成。其中,情感空间强调情感媒介设施、全龄友好空间和韧性情感设施营造,快乐空间可以分为快乐街道和沉浸式空间等,诗居空间突出文化守正创新、乡愁家园营建和空间美学塑造。因此,把握“心即理”的内涵,在认知层面完善国土空间规划的理论基础,从“心即理”探索国土空间规划的路径,有利于完善以人为本的国土空间规划的编制范式。

关键词：国土空间规划心即理认识论规划路径人本规划

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信息疫情中竞争性信息传播建模与实证研究

情报资料工作 2023年第1期44卷 62-71页

作者：王世雄朱明旻吴宜诺骆彦余浙江理工大学经济管理学院杭州310018 宁波大学商学院浙江315211

[目的/意义]文章厘清信息疫情中用户、行为和竞争性信息传播之间的作用关系,揭示信息疫情的生成和传播规律,为信息疫情干预政策的制定提供理论支撑。[方法/过程]文章以复杂网络理论为支撑,以新浪微博平台为参照,抽取用户、信息、行为之... 详细信息

[目的/意义]文章厘清信息疫情中用户、行为和竞争性信息传播之间的作用关系,揭示信息疫情的生成和传播规律,为信息疫情干预政策的制定提供理论支撑。[方法/过程]文章以复杂网络理论为支撑,以新浪微博平台为参照,抽取用户、信息、行为之间的关联作用机理,综合运用Logistic模型和行为博弈模型建立信息疫情竞争性信息传播模型,采用计算实验方法对模型进行验证。[结果/结论]研究表明,用户的原创、转发、评论行为均会影响用户对信息疫情的易感性以及信息疫情中真假信息的竞争性传播;重建用户行为秩序,引导用户生成高质量的真实信息,是帮助用户免受信息疫情影响的有效策略。

关键词：信息疫情竞争性传播用户行为计算实验