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Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity

Signal Transduction and Targeted Therapy 2024年第2期9卷 693-708页

作者： Tao Yuan Chenming Zeng Jiawei Liu Chenxi Zhao Fujing Ge Yuekang Li Meijia Qian Jiamin Du Weihua Wang Yonghao Li Yue Liu Xiaoyang Dai Jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang Institute of Pharmacology&Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in medicine Zhejiang UniversityHangzhou 311199China Ministry of Education Key Laboratory of chinese Medicinal Plants resource from Lingnan Research Center of Medicinal Plants Resource Science and EngineeringGuangzhou University of Chinese MedicineGuangzhou 510006China center for Drug Safety Evaluation and research of Zhejiang University Hangzhou 310058China Department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310006China Department of Oncology Hangzhou Cancer HospitalHangzhou 310002China Cancer center of Zhejiang University HangzhouChina engineering research center of Innovative Anticancer Drugs Ministry of EducationHangzhouChina

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths *** the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC ***,the need for novel strategies addressing NSCLC remains ***(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic ***,the mechanisms by which DUBs promote NSCLC remain poorly *** a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of *** of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in ***,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 ***,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in *** findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

关键词： LKB1 inhibiting removing

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Crocus genome reveals the evolutionary origin of crocin biosynthesis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1878-1891页

作者： Zhichao Xu Shanshan Chen Yalin Wang Ya Tian Xiaotong Wang Tianyi Xin Zishan Li Xin Hua Shengnan Tan Wei Sun Xiangdong Pu Hui Yao Ranran Gao Jingyuan Song Key Lab of chinese medicine resources Conservation State Administration of Traditional Chinese Medicine of the People's Republic of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China State Key Laboratory of Basis and New Drug Development of Natural and Nuclear Drugs Engineering Research Center of Chinese Medicine ResourceMinistry of EducationBeijing 100193China College of Life Science Northeast Forestry UniversityHarbin 150040China Key Laboratory of Beijing for Identification and Safety Evaluation of chinese medicine China Academy of Chinese Medical SciencesInstitute of Chinese Materia MedicaBeijing 100700China Analysis and Testing center of Northeast Forestry University Harbin 150040China School of Pharmacy Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui ProvinceHefei 230032China

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

关键词： Crocus sativus WGT Crocin biosynthesis Carotenoids Apocarotenoids CCDs

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Strategies on biosynthesis and production of bioactive compounds in medicinal plants

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chinese Herbal medicines 2024年第1期16卷 13-26页

作者： Miaoxian Guo Haizhou Lv Hongyu Chen Shuting Dong Jianhong Zhang Wanjing Liu Liu He Yimian Ma Hua Yu Shilin Chen Hongmei Luo Key Lab of chinese medicine resources Conservation State Administration of Traditional Chinese Medicine of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China engineering research center of chinese medicine resource Ministry of EducationBeijing 100193China Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration College of Life and Environmental SciencesHangzhou Normal UniversityHangzhou 311121China Chengdu University of traditional chinese medicine Chengdu 611137China

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease *** with chemical synthesis and extraction,the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants,and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal ***,we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal *** strategies and methods mainly include genetic engineering,plant cell culture engineering,metabolic engineering,and synthetic biology based on multiple“OMICS”technologies,with paradigms for the biosynthesis of terpenoids and *** also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products,exemplifying compounds such as vindoline(alkaloid),artemisinin and paclitaxel(terpenoids),to illustrate the power of biotechnology in medicinal plants.

关键词： biosynthetic strategies biotechnology natural products medicinal plants synthetic biology

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Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential

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Zoological research 2024年第5期45卷 1001-1012页

作者： Li-Na Cha Juan Yang Jin-Ai Gao Xin Lu Xiao-Long Chang Rebecca Caroline Thuku Qi Liu Qiu-Min Lu Dong-Sheng Li Ren Lai Ming-Qian Fang engineering Laboratory of Peptides of chinese Academy of Sciences Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Center for Non-Human PrimatesNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Key Laboratory of Genetic Evolution&Animal ModelsSino-African Joint Research Centerand New Cornerstone Science LaboratoryKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650201China School of Molecular medicine Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China First Affiliated Hospital of Kunming Medical University KunmingYunnan 650032China

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic *** contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionally with the coagulation and inflammation cascades,providing a novel target for therapeutic drug development in ischemic *** this study,we identified a bat-derived oligopeptide from Myotis myotis(Borkhausen,1797),designated LE6(Leu-Ser-Glu-Glu-Pro-Glu,702 Da),with considerable potential in stroke therapy due to its effects on the contact kinin ***,LE6 demonstrated significant inhibitory effects on PK and FXIIa,with inhibition constants of 43.97μmol/L and 6.37μmol/L,*** vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin *** murine models,LE6 effectively inhibited carrageenan-induced mouse tail thrombosis,FeCl3-induced carotid artery thrombosis,and photochemically induced intracerebral ***,LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion ***,the low toxicity,hemolytic activity,and bleeding risk of LE6,along with its synthetic simplicity,underscore its clinical *** conclusion,as an inhibitor of FXIIa and PK,LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

关键词： PK FXIIa Anti-thromboinflammation Ischemic stroke therapies Oligopeptide

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Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

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traditional medicine research 2024年第11期9卷 12-26页

作者： Jie-Hui Kuang Tao Hu Lu-Yong Zhang Yu-Feng Yao Ming-Hua Xian Shu-Mei Wang School of chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Key Laboratory of Digital Quality Evaluation of chinese Materia Medica of State Administration of traditional chinese medicine Guangdong Pharmaceutical UniversityGuangzhou 510006China engineering&Technology research center for chinese Materia Medica Quality of the Universities of Guangdong Province Guangdong Pharmaceutical UniversityGuangzhou 510006China Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems Guangdong Pharmaceutical UniversityGuangzhou 510006China traditional chinese medicine resource Germplasm Bank Management center Yunfu 527500China.

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac ***,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic *** objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat ***:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of *** integration of network pharmacology and metabolomics was conducted to investigate the *** docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated ***:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart *** results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for *** network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl ***:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

关键词： chronic myocardial ischemia metabolomics network pharmacology serum metabolites Shenzao dripping pill

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Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

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traditional medicine research 2024年第9期9卷 1-13页

作者： Ting Li Lan-Fang Tan Lin Shen Jie-Hui Kuang Si-Kai Zhan Bang Liu Jia-Le Cai Sheng-Wang Liang Ming-Hua Xian Shu-Mei Wang School of chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Key Laboratory of Digital Quality Evaluation of chinese Materia Medica of State Administration of TCM School of Chinese Materia MedicaGuangdong Pharmaceutical UniversityGuangzhou 510006China engineering&Technology research center for chinese Materia Medica Quality of the Universities of Guangdong Province School of Chinese Materia MedicaGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangxi Key Laboratory of Functional Phytochemicals research and Utilization Guangxi Institute of BotanyChinese Academy of SciencesGuilin 541006China traditional chinese medicine resource Germplasm Bank Management center Yunfu 527300China

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum *** Balf.)with millet *** is used as a traditional chinese medicine for treating cerebral stroke,where patients often face severe *** study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in *** used integrated analysis of gut microbiota,metabolomics,and network ***:The compounds in CR were identified using LC-MS/*** impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE *** in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also *** microbiota composition was analyzed through 16S rRNA gene *** metabolites were examined using untargeted metabolomics and Spearman correlation *** pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut ***:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction *** also ameliorates brain and intestinal barrier damage caused by *** also decreased inflammation and oxidative stress in IS ***,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier ***,CR primarily influences the primary bile acid biosynthesis *** pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential *** relies on gut microbiota for its anti-inflammatory effects to improve ***:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid *** emerges as a potential therapeutic agent for

关键词： cooked rhubarb ischemic stroke gut microbiota metabolomics

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Transferrin Is Up-Regulated by Microbes and Acts as a Negative Regulator of Immunity to Induce Intestinal Immunotolerance

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research 2024年第3期7卷 761-774页

作者： Xiaopeng Tang Mingqian Fang Ruomei Cheng Junkun Niu Xiaoshan Huang Kuanhong Xu Gan Wang Yang Sun Zhiyi Liao Zhiye Zhang James Mwangi Qiumin Lu Aili Wang Longbao Lv Chao Liu Yinglei Miao Ren Lai engineering Laboratory of Peptides of chinese Academy of Sciences Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Center for Non-Human PrimatesNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)and Sino-African Joint Research CenterNew Cornerstone Science InstituteKunming Institute of Zoologythe Chinese Academy of SciencesNo.17 Longxin RoadKunmingYunnan650201China School of Basic medicine Qingdao UniversityQingdao 266071ShandongChina. Department of Gastroenterology First Affiliated Hospital of Kunming Medical UniversityYunnan Institute of Digestive DiseaseKunming 650032YunnanChina Yunnan Province Clinical research center for Digestive Diseases Kunming 650032YunnanChina Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204YunnanChina Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences University of Science and Technology of ChinaHefei 230027AnhuiChina center for Evolution and Conservation Biology Southern Marine Science and Engineering Guangdong LaboratoryGuangzhou 511458GuangdongChina.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host’s tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin–CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

关键词： impaired immunity tolerance

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Polyaspers A and B,the First Ergosterol-Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus ***507

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chinese Journal of Chemistry 2024年第7期42卷 743-751页

作者： Hong Hu Lanqin Li Zhengyi Shi Xueqi Lan Yeting Zhang Xinye Huang Xincai Hao Qun Zhou Weiguang Sun Changxing Qi Yonghui Zhang Hubei Key Laboratory of Natural Medicinal Chemistry and resource Evaluation Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanHubei 430030China Hubei Key Laboratory of Wudang Local chinese medicine research Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal PlantsCollege of PharmacyHubei University of MedicineShiyanHubei 442000China

Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this *** our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus *** elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction *** A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder *** screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control *** bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT *** an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic *** such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.

关键词： Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease

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A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian Jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie Sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National engineering research center for Antibody medicine and Shanghai Key Laboratory of Cell engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

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Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

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Military Medical research 2024年第1期11卷 50-79页

作者： Shuai Liu Jiang-Ming Yu Yan-Chang Gan Xiao-Zhong Qiu Zhe-Chen Gao Huan Wang Shi-Xuan Chen Yuan Xiong Guo-Hui Liu Si-En Lin Alec McCarthy Johnson V.John Dai-Xu Wei Hong-Hao Hou Guangdong Provincial Key Laboratory of Construction and Detection in Tissue engineering the Fifth Affiliated HospitalSchool of Basic Medical ScienceSouthern Medical UniversityGuangzhou 510900China Department of Orthopedics Tongren HospitalShanghai Jiao Tong UniversityShanghai 200336China The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033GuangdongChina engineering research center of Clinical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325011ZhejiangChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Orthopaedics and Traumatology Faculty of Medicinethe Chinese University of Hong KongHong Kong SAR 999077China Department of Functional Materials Terasaki Institute for Biomedical InnovationLos AngelesCA 90064USA Mary&Dick Holland Regenerative medicine Program College of MedicineUniversity of Nebraska Medical CenterOmahaNE 68130USA Zigong Affiliated Hospital of Southwest Medical University Zigong Psychiatric Research CenterZigong Institute of Brain ScienceZigong 643002SichuanChina Key Laboratory of resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineDepartment of Life Sciences and MedicineNorthwest UniversityXi’an 710127China

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative *** contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative *** paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future *** highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ***,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE ***,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

关键词： Biomimic Scaffold Biosynthesis Natural biomaterial Tissue engineering

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