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Discovery of New Bohemamines and Synthesis of Methylene-Bridged Chimeric Derivatives through Natural Product Chimera Strategy

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Chinese Journal of Chemistry 2022年第12期40卷 1413-1421页

作者： Rongxin Zhang Xiaotang Yan Shupeng Yin Weihong Wang Weiming Zhu Peng Fu Key Laboratory of Marine Drugs Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdaoShandong 266003China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)QingdaoShandong 266237China

Five new pyrrolizidine alkaloids,bohemamines J—N(1-5),were isolated from Streptomyces sp.CPCC 200497.Their structures were assigned based on detailed spectroscopic analysis and semisynthesis.Bohemamine J(1)possesses a new chimeric skeleton derived from bohemamine A(6)and phenylacetaldehyde.Inspired by the nonenzymatic formation mechanism of the methylene-bridged dimers isolated from this strain,we synthesized a series of chimeric derivatives(8,9,and 12-23)through natural product chimera strategy.Compounds 13,15,19,and 21 showed significant antioxidant activity.

关键词： Natural products Structure elucidation Dimerization Pyrrolizidine alkaloids Biological activity

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

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Nano Research 2024年第3期17卷 1748-1759页

作者： Zhenxing zhu Dongtao Zhou Yi Yin zhun Li Zhen Guo Yongchun Pan Yanfeng Gao Jingjing Yang Weiming Zhu Yujun Song Yi Li Department of General Surgery Affiliated Jinling HospitalMedical SchoolNanjing UniversityNanjing 210093China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Department of General Surgery Affiliated Drum Tower HospitalMedical SchoolNanjing UniversityNanjing 210008China Department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineJiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Inflammatory bowel disease(IBD)is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the intestine.Excessive pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in IBD.Here,we designed an oral pyroptosis nanoinhibitor,DXMS@CuM@PPADT@PSS(DCMP),which can target intestinal lesions,and respond to reactive oxygen species(ROS)to release active sites and drugs at the lesion.DCMP can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3(NLRP3)inflammasomes by scavenging ROS,resulting in the down-regulation of gasdermin D(GSDMD)cleavage thus inhibiting pyroptosis.It also improved intestinal barrier function,decreased inflammatory cytokine levels,and increased the diversity of gut microbiota in mice with colitis.This work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

关键词： inflammatory bowel disease nanoinhibitors pyroptosis synergistic therapy antioxidant

(±)-Pyriindolin with a 2,2'-bipyridine-spiro[furan-3,3'-indoline]chimeric skeleton from the endophytic Streptomyces albolongus EA12432

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Chinese Chemical Letters 2022年第1期33卷 508-510页

作者： Mengmeng Lan Tongxu Cui Kaichun Xia Guodong Cui Yiwen Chu Peng Fu Weiming Zhu Key Laboratory of Marine Drugs Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China School of Pharmacy Chengdu UniversityChengdu 610106China

(±)-Pyriindolin(1)with a rare molecular backbone formed by fusing a 2,2'-bipyridine nucleus into a spiro[furan-3,3'-indoline]skeleton,was isolated from the Streptomyces albolongus EA12432.The constitution and the relative configuration of(±)-1 were determined by extensive spectroscopic analyses,^(13)C calculation and DP4+probability analysis.The absolute configurations of optically pure(+)-1 and(-)-1 which were obtained after a chiral high performance liquid chromatography(HPLC)separation were further identified by electronic circular dichroism(ECD)calculations.(+)-and(-)-Pyriindolins displayed moderate cytotoxicity against HCT-116 cell line with the half-maximal inhibitory concentration(IC_(50))values of 2.89±0.17μmol/L and 4.47±0.26μmol/L,respectively.

关键词： Pyrisulfoxins Spiroindolone Streptomyces sp. Endophyte Cytotoxicity

p-Terphenyl alcohols from a marine sponge-derived fungus, Aspergillus candidus OUCMDZ-1051

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Marine Life Science & Technology 2020年第3期2卷 262-267页

作者： Dongyang Wang Peng Qu Jiayu Zhou Yi Wang Liping Wang Weiming Zhu Key Laboratory of Marine Drugs Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Open Studio for Druggability Research of Marine Natural Products.Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266003China State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550014China

In order to discover structurally new and bioactive conipounds from marine life,we studied the secondary metabolites of the marine-derived fungi associated with a marine sponge(XS-3)from the Xisha islands.As a result,4-O-methylcandidusin A(1),a new p-terphenyl alcohol,along with nine known analogs(2-10),were isolated and identified from the marine spongederived fungus Aspergillus candidus OUCMDZ-1051.The structures of these compounds were determined by analyzing spectroscopic data,especially ID and 2D NMR.The new compound 1 selectively inhibited the growth of the MDA-MB-46&BT474 and A431 human cancer cell lines with the IC_(50) values of 1.84,6.05 and 0.98 pmol/L,respectively.Compound 1 also displayed a selective antimicrobial activity against Escherichia coli with an MIC value of 27.3 pmol/L.The results indicated 4-O-methylcandidusin A(1)as a potential lead in the new drug discovery for triple negative breast cancer,invasive ductal breast cancer and epidermoid cancer.The antimicrobial metabolites also evidenced a clue for chemical defense of sponges by their associated microorganisms.

关键词： Sponge-derived fungus Aspergillus candidus Natural products p-Terphenyl Cytotoxicity Antimicrobial activity

Versatile band structure and electron-phonon coupling in layered PtSe_(2) with strong interlayer interaction

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Nano Research 2022年第7期15卷 6613-6619页

作者： Junbo He Xudan zhu weiming Liu Ertao Hu Jianlu Wang Rongjun Zhang Department of Optical Science and Engineering Fudan UniversityShanghai 200433China College of Electronic and Optical Engineering Nanjing University of Posts and TelecommunicationsNanjing 210023China Institute of Optoelectronics Fudan UniversityShanghai 200433China Academy for Engineering and Technology Fudan UniversityShanghai 200433China Yiwu Research Institute of Fudan University Yiwu 322000China

The large tunability in the band structure is ubiquitous in two-dimensional(2D)materials,and PtSe_(2) is not an exception,which has attracted considerable attention in electronic and optoelectronic applications due to its high carrier mobility and long-term airstability.Such dimensional dependent properties are closely related to the evolution of electronic band structures.Critical points(CPs),the extrema or saddle points of electronic bands,are the cornerstone of condensed-matter physics and fundamentally determine the optical and transport phenomena of the layered PtSe_(2).Here,we have experimentally revealed the detailed electronic structures in layered PtSe_(2),including the CPs in the Brillouin zones(BZs),by means of reflection contrast spectroscopy and spectroscopic ellipsometry(SE).There are three critical points in the BZs attributed to the excitonic transition,quasi-particle band gap,and the band nesting effect related transition,respectively.Three CPs show red-shifting trends with increasing layer number under the mechanism of strong interlayer coupling.We have further revealed the electron–phonon(e–ph)interaction in such layered material,utilizing temperature-dependent absorbance spectroscopy.The strength of e–ph interaction and the average phonon energy also decline with the increasement of layer number.Our findings give a deep understanding to the physics of the layer-dependent evolution of the electronic structure of PtSe_(2),potentially leading to applications in optoelectronics and electronic devices.

关键词： layered transition metal dichalcogenides PtSe_(2)thin films interlayer coupling critical points electron-phonon interaction

Pafuranones A and B, two dimeric polyketides from a rare marine algae-derived fungus Paraconiothyrium sp.

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Chinese Chemical Letters 2019年第5期30卷 981-984页

作者： Yuqi Du Zhengbo Chen Hao Li Yi Wang Peng Fu Weiming Zhu Key Laboratory of Marine Drugs Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology Qingdao 266003China

Pafuranones A(1)and B(2),a pair of new epimeric polyketide dimers,were isolated from the fungus Paraconiothyrium sp.OUCMDZ-3316 associated with the marine algae Enteromorpha prolifera.Their structures,including absolute configurations,were fully elucidated based on spectroscopic analysis,calculated ECD,and chemical methods.Pafuranones A(1)and B(2)possess a rare dimeric furanone skeleton,which might be formed through a conjugate addition of the monomeric units followed by an intramolecular cyclization.

关键词： Pafuranone Dimer Fungus Paraconiothyrium sp. Enteromorpha prolifera

Constrained geometry analysis to resolve 3-D deformations from three ground-based radars

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Journal of Systems Engineering and Electronics 2021年第6期32卷 1263-1269页

作者： DENG Yunkai zhu Jiaxin TIAN weiming HU Cheng YANG Wenyu Radar Research Lab School of Information and ElectronicsBeijing Institute of TechnologyBeijing 100081China Key Labo-ratory of Electronic and Information Technology in Satellite Navigation Ministry of EducationBeijing Institute of TechnologyBeijing 100081China Chongqing Key Laboratory of Geological Environment Monitoring and Disaster Early-warning in Three Gorges Reservoir Area Chongqing Three Gorges UniversityChongqing 404000China Advanced Technology Research Insti-tute Beijing Institute of TechnologyJi’nan 250300China Beijing Institute of Technology Chongqing Innovation Center Chongqing 401120China

When multiple ground-based radars(GB-rads)are utilized together to resolve three-dimensional(3-D)deformations,the resolving accuracy is related with the measurement geometry constructed by these radars.This paper focuses on constrained geometry analysis to resolve 3-D deformations from three GB-rads.The geometric dilution of precision(GDOP)is utilized to evaluate 3-D deformation accuracy of a single target,and its theoretical equation is derived by building a simplified 3-D coordinate system.Then for a 3-D scene,its optimal accuracy problem is converted into determining the minimum value of an objective function with a boundary constraint.The genetic algorithm is utilized to solve this constrained optimization problem.Numerical simulations are made to validate the correctness of the theoretical analysis results.

关键词： three-dimensional(3-D)deformation ground-based radar(GB-rad) constrained geometry geometric dilution of precision(GDOP) accuracy evaluation

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

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Neural Regeneration Research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National Clinical Research Center for Geriatric Diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye Center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

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难治性肛周克罗恩病处理面临的挑战

中华炎性肠病杂志（中英文） 2023年第3期7卷 209-213页

作者：朱维铭南京大学医学院附属金陵医院(东部战区总医院)普通外科南京210002

难治性肛周克罗恩病(CD)是CD治疗的难点,也是影响患者生活质量的重要因素。由于病情复杂,治疗困难,在治疗规范上还缺乏一致意见。本文概括了难治性肛周CD内科治疗和外科治疗的基本要点和总原则,强调多学科团队(MDT)在治疗过程中的作用... 详细信息

难治性肛周克罗恩病(CD)是CD治疗的难点,也是影响患者生活质量的重要因素。由于病情复杂,治疗困难,在治疗规范上还缺乏一致意见。本文概括了难治性肛周CD内科治疗和外科治疗的基本要点和总原则,强调多学科团队(MDT)在治疗过程中的作用以及转流性肠造口和结直肠切除术中应把握的基本原则,旨在提高治疗效果和患者的生活质量。

关键词：克罗恩病肛周难治性多学科团队外科治疗肠造口术转流性生物制剂