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Genetically engineered materials:Proteins and beyond

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Science China Chemistry 2022年第3期65卷 486-496页

作者： Jingjing Wei Lianjie Xu wen-hao wu Fei Sun wen-Bin Zhang College of Chemical and Environmental Engineering Anyang Institute of TechnologyAnyang 455000 China 2.Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry&Physics of Ministry of EducationCenter for Soft Matter Science and EngineeringCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871 China 3.Department of Chemical and Biological Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong SARChina

Information-rich molecules provide opportunities for evolution.Genetically engineered materials are superior in that their properties are coded within genetic sequences and could be fine-tuned.In this review,we elaborate the concept of genetically engineered materials(GEMs)using examples ranging from engineered protein materials to engineered living materials.Proteinbased materials are the materials of choice by nature.Recent progress in protein engineering has led to opportunities to tune their sequences for optimal material performance.Proteins also play a central role in living materials where they act in concert with other biological components as well as nonbiological cofactors,giving rise to living features.While the existing GEMs are often limited to those constructed by building blocks of biological origin,being genetically engineerable does not preclude nonbiologic or synthetic materials,the latter of which have yet to be fully explored.

关键词： protein genetic engineering self-assembly living materials

Post-Newtonian binary dynamics in the effective field theory of Horndeskigravity

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Chinese Physics C 2024年第3期48卷 180-190页

作者：武文浩汤勇 School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyChinese Academy of SciencesHangzhou 310024China International Center for Theoretical Physics Asia-Pacific Beijing 100049China

General relativity has been very successful since its proposal more than a century ago.However,various cosmological observations and theoretical consistency still motivate us to explore extended gravity theories.Horndeski gravity stands out as one attractive theory by introducing only one scalar field.Here we formulate the post-Newtonian effective field theory of Horndeski gravity and investigate the conservative dynamics of inspiral compact binary systems.We calculate the leading effective Lagrangian for a compact binary and obtain the periastron advance per period.In particular,we apply our analytical calculation to two binary systems,PSR B 1534+12 and PSR J0737-3039,and constrain the relevant model parameters.This theoretical framework can also be systematically extended to higherorders.

关键词： effective field theory modified gravity pulsar

A Moonlighting Superpositively Charged SpyCatcher

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CCS Chemistry 2023年第11期5卷 2663-2673页

作者： Tingting Yang Yajie Liu wen-hao wu Rongmei Peng wen-Bin Zhang Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry and Physics of Ministry of EducationCenter for Soft Matter Science and EngineeringCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871 Key Laboratory of Vision Loss and Restoration Ministry of EducationBeijing 100084 Department of Ophthalmology Peking University Third HospitalBeijing 100191 Beijing Academy of Artificial Intelligence Beijing 100084

Genetically encoded covalent peptide tagging tools such as the SpyTag/SpyCatcher reactive pair,have been demonstrated versatile and useful for protein modification.Herein,we present a superpositively charged SpyCatcher bearing a theoretical net charge of+21 capable of accomplishing multiple unrelated independent tasks to enrich this toolbox and cultivate new functions.The SpyCatcher(+21)possessed stimuli-responsive reactivity toward SpyTag and could serve as a potent and general platform for the delivery of proteins,including RNaseAinto HeLa cells.Remarkably,the delivered RNase A caused substantial proliferation inhibition toward HeLa cells.In addition,the superpositively charged SpyCatcher could form coacervate with plasmid DNA for further study of gene delivery and liquid–liquid phase separation.These findings demonstrate the robustness of the SpyTag/SpyCatcher structure against surface mutation and the prospect of applying supercharging technology on diverse functional proteins to create moonlighting proteins.

关键词： SpyCatcher stimuli-responsive protein delivery phase separation supercharging cyclic proteins topology

Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling

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World Journal of Gastrointestinal Oncology 2022年第1期14卷 253-264页

作者： Wei Zheng Guo-Liang Shen Ke-Yang Xu Qiao-Qiao Yin Tian-Chen Hui Zhe-wen Zhou Cheng-An Xu Shou-hao Wang wen-hao wu Ling-Fei Shi Hong-Ying Pan Department of Clinical Medicine Medical College of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Infectious Diseases Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310014Zhejiang ProvinceChina Department of Hepatobiliary&Pancreatic Surgery and Minimally Invasive Surgery Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310014Zhejiang ProvinceChina School of Chinese Medicine Hongkong Baptist universityHong Kong 999777China Department of Graduate School Bengbu Medical CollegeBengbu 233030Anhui ProvinceChina Second Clinical Medical College Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina Medical Department of Qingdao University Qingdao UniversityQingdao 266071ShandongChina Diagnosis and Treatment Center of Osteoporosis Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHang Zhou 310014Zhejiang ProvinceChina

BACKGROUND Liver cancer is one of the most highly malignant cancers,characterized by easy metastasis and chemoradiotherapy resistance.Emerging evidence indicates that long noncoding RNAs(LncRNAs),including Lnc524369,are highly involved in the initiation,progression,radioresistance,and chemoresistance of hepatocellular carcinoma(HCC).However,the function of Lnc524369 remains unclear.AIM To explore the function of Lnc524369 in HCC.METHODS To investigate the effect of Lnc524369,tissue from 41 HCC patients were analyzed using CCK8,migration,and invasion assays.Lnc524369 and YWHAZ(also named 14-3-3ζ)mRNA were detected by qPCR,and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues.The Cancer Cell Line Encyclopedia(CCLE)databases,STRING database,Human Protein Atlas database,and the TCGA database were used for bioinformatic analysis.RESULTS Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues.Overexpression of Lnc524369 was associated with the proliferation,migration,and invasion of liver cancer cells.YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer,which could be attenuated by overexpression of Lnc524369.Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time.CONCLUSION Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

关键词： Long noncoding RNAs Lnc524369 Hepatocellular carcinoma YWHAZ RAF1

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教育学自主知识体系的本质特征和建构规律

西北师大学报（社会科学版） 2024年第1期61卷 77-85页

作者：郝文武陕西师范大学教育学部陕西西安710062

教育学自主知识体系是教育主体自主建构的全面深入反映教育本质和规律的知识系统;是在海内外文化、不同学科知识相互影响、交融中形成的知识体系;是合目的与合规律、价值追求与思维逻辑统一的知识体系;是继承与发展、守正与创新结合形... 详细信息

教育学自主知识体系是教育主体自主建构的全面深入反映教育本质和规律的知识系统;是在海内外文化、不同学科知识相互影响、交融中形成的知识体系;是合目的与合规律、价值追求与思维逻辑统一的知识体系;是继承与发展、守正与创新结合形成的知识体系。这既是教育学自主知识体系的本质,也决定了它形成的规律和原则、方式、途径。

关键词：教育学自主知识体系本质特征建构规律

Diagnosis and treatment of an inborn error of bile acid synthesis type 4:A case report

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World Journal of Clinical Cases 2021年第26期9卷 7923-7929页

作者： Shou-hao Wang Tian-Chen Hui Zhe-wen Zhou Cheng-An Xu wen-hao wu Qing-Qing wu Wei Zheng Qiao-Qiao Yin Hong-Ying Pan Zhejiang Provincial People’s Hospital Qingdao UniversityHangzhou 310014Zhejiang ProvinceChina Department of Infectious Diseases Zhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou 310014Zhejiang ProvinceChina

BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.

关键词： Bile acid synthesis A-methylacyl-CoA racemase gene Gene mutation Inborn error of metabolism Ursodeoxycholic acid Case report

Pneumocystis jirovecii and Legionella pneumophila coinfection in a patient with diffuse large B-cell lymphoma:A case report

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World Journal of Clinical Cases 2021年第28期9卷 8595-8601页

作者： wen-hao wu Tian-Chen Hui Qing-Qing wu Cheng-An Xu Zhe-wen Zhou Shou-hao Wang Wei Zheng Qiao-Qiao Yin Xi Li Hong-Ying Pan Department of Infectious Diseases Zhejiang Provincial People’s HospitalHangzhou 310014Zhejiang ProvinceChina Medical College Qingdao UniversityQingdao 266071Shandong ProvinceChina Centre of Laboratory Medicine Zhejiang Provincial People’s HospitalHangzhou 310014Zhejiang ProvinceChina

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common non-Hodgkin's lymphoma.R-CHOP is a protocol for long-term chemotherapy for DLBCL patients.Longterm chemotherapy can lead to low immunity and increase the risk of opportunistic pathogen infections in immunocompromised patients.CASE SUMMARY We report a case of coinfection with Pneumocystis jirovecii(P.jirovecii)and Legionella pneumophila(L.pneumophila)in a patient with DLBCL.The patient was a 40-year-old female who was diagnosed with DLBCL and was admitted due to pulmonary infection.P.jirovecii and L.pneumophila were detected in her bronchoalveolar lavage fluid by hexamine silver staining,isothermal amplification and metagenomic sequencing.CONCLUSION To the best of our knowledge,this is the first case of P.jirovecii and L.pneumophila coinfection found in a DLBCL patient.Clinicians should be aware of the risk of complicated infection in patients undergoing long-term chemotherapy.

关键词： Legionella pneumophila Pneumocystis jirovecii Next-generation sequencing Diffuse large B-cell lymphoma Case report

Native conjugation between proteins and [60]fullerene derivatives using SpyTag as a reactive handle

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Chinese Chemical Letters 2021年第1期32卷 353-356页

作者： Guangzhong Yin Jingjing Wei Yu Shao wen-hao wu Lianjie Xu wen-Bin Zhang Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry and Physics of the Ministry of EducationCollege of Chemistry and Molecular EngineeringCenter for Soft Matter Science and EngineeringPeking UniversityBeijing 100871China College of Chemical and Environmental Engineering Anyang Institute of TechnologyAnyang 455000China

Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were first prepared via sequential Bingel-Hirsch reaction and "clicked" with SpyTag to give DC_(60)-SpyTag for native conjugation with proteins by the highly efficient SpyTag-SpyCatcher chemistry.The bioconjugation was confirmed by MALDI-TOF MS spectra and SDS-PAGE analysis.The TEM and UVvis spectroscopic study further revealed that the DC_(60) could alter the optical performance and induce aggregation of the target proteins.It thus provides a general and robust method for modifying proteins with C_(60) derivatives and could potentially be adapted for native conjugation between proteins and other nonbiological motifs as well.

关键词： SpyTag Spy Catcher Fullerene Protein Bioconjugate

Reversible hydrogels with tunable mechanical properties for optically controlling cell migration

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Nano Research 2018年第10期11卷 5556-5565页

作者： Xin wu wenmao Huang wen-hao wu Bin Xue Dongfang Xiang Ying Li Meng Qin Fei Sun Wei Wang wen-Bin Zhang Yi Cao Collaborative Innovation Center of Advanced Microstructures National Laboratory of Solid State Microstructure and Department of Physics Nanjing University Nanjing 210093 China Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College ot Chemistry and Molecular Engineering Peking University Beijing 100871 China Collaborative Innovation Center of Atmospheric Environment and Equipment Technology School of Environmental Science and Engineering Nanjing University olin formation Science & Technology Nanjing 210044 China Department of Chemical and Biomolecular Engineering Division of BioMedical Engineering and Center for Systems Biology & Human Health The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong China

Synthetic hydrogels are widely used as biomimetic in vitro model systems to understand how cells respond to complex microenvironments. The mechanical properties of hydrogels are deterministic for many cellular behaviors, including cell migration, spreading, and differentiation. However, it remains a major challenge to engineer hydrogels that recapture the dynamic mechanical properties of native extracellular matrices. Here, we provide a new hydrogel platform with spatiotemporally tunable mechanical properties to assay and define cellular behaviors under light. The change in the mechanical properties of the hydrogel is effected by a photo-induced switch of the cross-linker fluorescent protein, Dronpa145N, between the tetrameric and monomeric states, which causes minimal changes to the chemical properties of the hydrogel. The mechanical properties can be rapidly and reversibly tuned for multiple cycles using visible light, as confirmed by rheological measurements and atomic force microscopy- based nano-indentation. We further demonstrated real-time and reversible modulation of cell migration behaviors on the hydrogels through photo-induced stiffness switching, with minimal invasion to the cultured cells. Hydrogels with a programmable mechanical history and a spatially defined mechanical hierarchy might serve as an ideal model system to better understand complex cellular functions.

关键词： Dronpa photo-responsive hydrogel mechanical properties cell migration artificial extracellular matrix