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Chinese Journal of Chemistry 2024年第12期42卷 1341-1346页

作者： Haoliang Shi Yi Wan Yongqiang Zhang shanghai frontiers science center of optogenetic techniques for cell metabolism Shanghai Key Laboratory of New Drug Designand School of PharmacyEast China University of Science and TechnologyShanghai200237 China

The divergent synthesis of versatile 3,3′-disubstituted oxetane amino acids by utilizing visible-light-induced photocatalytic decarboxylative Giese-type reaction has been demonstrated.3-Methyleneoxetane-derived substrates are readily available in a single-step and highly reactive as radical acceptors,allowing the production of versatile oxetaneγ-andα-amino acids in high yields.A distinct ring strain release-driven radical addition mechanism was preliminarily *** preparative power was further highlighted by the application in the synthesis of oxetane-containing dipeptides and azetidine amino acids,as well as the transformation of the product into novel oxetane-containing spiro-heterocycle pharmacophore.

关键词： Photoredox catalysis Decarboxylative Giese-type reaction Oxetane amino acids Amino acids Synthesis Radical reactions

Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent

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Acta Pharmaceutica Sinica B 2024年第2期14卷 729-750页

作者： Xin Chen Xianggang Mu Lele Ding Xi Wang Fei Mao Jinlian Wei Qian Liu Yixiang Xu Shuaishuai Ni Lijun Jia Jian Li State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismFrontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China College of Pharmacy Jinan UniversityGuangzhou 510632China

Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer *** intertwined adverse effects,brought by cancer and its complication,further complicate anticancer therapy and lead to diminished clinical *** supplementation of cardioprotective agents falls short in addressing these *** bifunctional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events *** repurposing was naturally endowed with co-therapeutic potential of two indications,implying a unique chance in the development of bi-functional ***,we further proposed a novel“trilogy of drug repurposing”strategy that comprises function-based,targetfocused,and scaffold-driven repurposing approaches,aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional *** function-based repurposing,a cardioprotective agent,carvedilol(CAR),was identified as a potential neddylation inhibitor to suppress lung cancer *** target-focused SAR studies and scaffold-driven drug design,we synthesized 44 CAR derivatives to achieve a balance between anticancer and ***,optimal derivative 43 displayed promising bi-functional effects,especially in various self-established heart failure mice models with and without ***,the present study validated the practicability of the“trilogy of drug repurposing”strategy in the development of bi-functional cotherapy agents.

关键词： Anticancer Heartfailure Complication Drug repurposing Bi-functional drug

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生物材料介观结构组装及工程化的最新进展、挑战和前景

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science China Materials 2024年第8期67卷 2462-2468页

作者：焦芸可雷淼唱荣航屈雪 Key Laboratory for Ultrafine Materials of Ministry of Education School of Material Science and EngineeringFrontiers Science Center for Materiobiology and Dynamic ChemistryEast China University of Science and TechnologyShanghai 200237China Wenzhou Institute of shanghai University Wenzhou 325000China shanghai frontier science center of optogenetic techniques for cell metabolism Shanghai 200237China

尽管天然生物组织的组分性能有限,但其跨越多尺度的复杂有序结构赋予了其出色的功能,这一点在介观尺度尤为显著.介观结构在调控材料的物理性质和生物活性方面发挥着至关重要的作用.本文深入探讨了对组织再生修复材料进行介观结构控制的... 详细信息

尽管天然生物组织的组分性能有限,但其跨越多尺度的复杂有序结构赋予了其出色的功能,这一点在介观尺度尤为显著.介观结构在调控材料的物理性质和生物活性方面发挥着至关重要的作用.本文深入探讨了对组织再生修复材料进行介观结构控制的挑战,并提出了一种新型的场调控动态自组装技术.该技术以电化学沉积技术为基础,通过调控电化学参数或与其他物理场进行耦合,能够更精准地控制生物大分子组装体的介观结构,从而实现材料的高性能化.此外,本文还讨论了该技术在工程化应用上的优势.最后强调了跨学科和跨部门合作的重要性,这对于推动生物材料制造技术的产业化和商业化至关重要.总之,该技术在组织再生领域展现出了广阔的发展前景.

关键词：电化学参数组织再生介观结构跨部门合作介观尺度电化学沉积物理场工程化

Open-vessel Synthesis of Poly-N-methoxyethylglycine

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Chemical Research in Chinese Universities 2024年第1期40卷 153-158页

作者： LIU Guojan MA Ke CHEN Qi ZHANG Donghui LIU Runhui State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai200237P.R.China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237P.R.China School of Biotechnology East China University of Science and TechnologyShanghai200237P.R.China

Polypeptoids are widely used in biological applications owing to their diverse functions and proteolytic *** type of polypeptoids,poly-N-methoxyethylglycine(P-Nmeg),has been found to possess remarkable hydrophilicity and notable properties in terms of protein,cell,and bacterial ***,the currently known synthesis methods of P-Nmeg include solid-phase synthesis,which is time-consuming and difficult to scale up,and N-substituted N-carboxyanhydride(NNCA)ring-opening polymerization,whose monomers were difficult to *** this study,we used the chemical stable Nmeg N-phenoxycarbonyl(NPC)as the monomer,which was obtained without the use of highly toxic reactants,such as phosgene or phosphorus halide,to synthesize P-Nmeg under open-vessel *** adding BnNH_(2) as an initiator at 80℃,we can obtain controllable short chain length P-Nmeg with narrow dispersity.

关键词： Open-vessel Polypeptoid synthesis Poly-N-methoxyethylglycine Stable monomer Narrow dispersity

Fluorogenic sensing of amorphous aggregates,amyloid fibers,and chaperone activity via a near-infrared aggregation-induced emission-active probe

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Aggregate 2024年第1期5卷 309-320页

作者： Wei He Yuanyuan Yang Yuhui Qian Zhuoyi Chen Yongxin Zheng Wenping Zhao Chenxu Yan Zhiqian Guo Shu Quan State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing(SCICB)East China University of Science and TechnologyShanghaiChina Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials ChemistryFrontiers Science Center for Materiobiology and Dynamic ChemistryInstitute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChina shanghai frontiers science center of optogenetic techniques for cell metabolism East China University of Science and TechnologyShanghaiChina

The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these *** the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates,there is still a lack of tools capable of simultaneously detecting both types of ***,we demonstrate the quantitative discernment of amorphous aggregates by QM-FN-SO3,an aggregationinduced emission(AIE)probe initially designed for detecting amyloid *** probe easily penetrates the membranes of the widely-used prokaryotic model organism Escherichia coli,enabling the visualization of both amorphous aggregates and amyloid fibers through near-infrared ***,the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins,regardless of whether they form amorphous aggregates or amyloid fibers in *** properties contribute to the successful application of the QM-FN-SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein(OMP)chaperones,both in vitro and in their physiological ***,our work introduces a near-infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in ***,it demonstrates the applicability of the probe in chaperone biology and its potential as a high-throughput screening tool for protein aggregation inhibitors and folding factors.

关键词： aggregation-induced emission fluorescence molecular chaperone protein aggregation

Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications

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Asian Journal of Pharmaceutical sciences 2024年第1期19卷 1-17页

作者： Jiafeng Zou Zeting Yuan Xiaojie Chen You Chen Min Yao Yang Chen Xiang Li Yi Chen Wenxing Ding Chuanhe Xia Yuzheng Zhao Feng Gao shanghai frontier science Research Base of optogenetic techniques for cell metabolism School of PharmacyEast China University of Science and TechnologyShanghai 200237China Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China shanghai Key Laboratory of Functional Materials Chemistry East China University of Science and TechnologyShanghai 200237China shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China optogenetics and Synthetic Biology Interdisciplinary Research center State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghai 200237China CAS center for Excellence in Brain science Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Research Unit of New techniques for Live-cell Metabolic Imaging Chinese Academy of Medical SciencesBeijing 100050China

Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas *** studies have mainly focused on the production and pharmacological side effects caused by H_(2)***,effective strategies to remove H_(2)S has become a key research ***,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)*** paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and ***,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were *** only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this ***,this review provided in-depth analysis of the potential of HRNs about treatment or detection in ***,potential challenges of HRNs were *** study demonstrates the excellent potential of HRNs for biomedical applications.

关键词： Hydrogen sulfide Disease mechanisms Removal of hydrogen sulfide Responsive nanoplatforms Challenges Biomedical applications

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang Laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University frontier science center for Stem cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical science Wenzhou Medical University Institute of Life sciences College of Life and Environmental Sciences Wenzhou University optogenetics&Synthetic Biology Interdisciplinary Research center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

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science China(Life sciences) 2024年第5期67卷 1035-1050页

作者： Yaling Wang Jingwen Chen Xueying Huang Bangguo Wu Peng Dai Feng Zhang Jinsong Li Lingbo Wang State Key Laboratory of Genetic Engineering Shanghai Key Laboratory of Metabolic Remodeling and HealthInstitute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(shanghai Institute for Biomedical and Pharmaceutical Technologies) School of PharmacyFudan UniversityShanghai 200433China shanghai Key Laboratoryof Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchoolof Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced *** enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for ***,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona *** further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO *** ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar *** study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.

关键词： disease modeling infertility multiple morphological abnormalities of the flagella(MMAF) induction of STOP-codons(iSTOP CRISPR-STOP) sperm motility

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模拟宿主防御肽的聚(2-噁唑啉)作为佐剂增强多粘菌素B的抗菌活性并拓展抗菌谱

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science China Materials 2024年第3期67卷 991-999页

作者：罗政杰赵学斌周敏邹景橙肖希勉刘龙强谢佳洋武月铭张雯静刘润辉 State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China shanghai frontiers science center of optogenetic techniques for cell metabolism Key Laboratory for Ultrafine Materials of Ministry of EducationFrontiers Science Center for Materiobiology and Dynamic ChemistryResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Orthopedic Surgery Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China

临床上常用的广谱抗生素无法有效解决抗生素高度耐药ESKAPE菌感染的难题,ESKAPE耐药菌已经成为人类生命健康的重大威胁.抗生素与佐剂的联合治疗是解决抗生素耐药菌感染的重要途径,但是探索对所有ESKAPE耐药菌都具有广谱和高效抗菌活性... 详细信息

临床上常用的广谱抗生素无法有效解决抗生素高度耐药ESKAPE菌感染的难题,ESKAPE耐药菌已经成为人类生命健康的重大威胁.抗生素与佐剂的联合治疗是解决抗生素耐药菌感染的重要途径,但是探索对所有ESKAPE耐药菌都具有广谱和高效抗菌活性的抗生素-佐剂组合仍然面临巨大挑战.在这里,我们提出了一种抗生素-佐剂的有效设计策略,将对ESKAPE中耐药阴性菌具有高活性的多粘菌素B(PMB)与模拟宿主防御肽的细菌膜靶向阳离子聚(2-噁唑啉)相结合.我们通过2-噁唑啉单体可控聚合,合成了一系列具有不同疏水性侧链的阳离子聚(2-噁唑啉).研究表明,聚(2-噁唑啉)和PMB的组合效果随着聚(2-噁唑啉)侧链疏水性的提高呈现出从拮抗效应到协同效应的逐渐变化.其中,优选的聚(2-噁唑啉)EACA-POX_(20)显著增强了PMB的抗菌活性,尤其是对于ESKAPE耐药阳性菌的抗菌活性增强了16–32倍.聚(2-噁唑啉)EACA-POX_(20)有效增强了PMB的抗菌活性并扩展了PMB的抗菌谱.聚(2-噁唑啉)和PMB的组合策略能够有效对抗所有耐药ESKAPE病原体,为解决ESKAPE耐药菌提供了新的思路.

关键词： poly(2-oxazoline)s ESKAPE bacteria polymyxin B broad-spectrum activity

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生物材料介观结构组装及工程化的最新进展、挑战和前景（英文）

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science China Materials 2024年

作者：焦芸可雷淼唱荣航屈雪 shanghai frontier science center of optogenetic techniques for cell metabolism Wenzhou Institute of shanghai University Key Laboratory for Ultrafine Materials of Ministry of Education School of Material Science and Engineering Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and Technology

尽管天然生物组织的组分性能有限,但其跨越多尺度的复杂有序结构赋予了其出色的功能,这一点在介观尺度尤为显著.介观结构在调控材料的物理性质和生物活性方面发挥着至关重要的作用.本文深入探讨了对组织再生修复材料进行介观结构控制的...

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