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Spy chemistry enables stable protein immobilization on iron oxide nanoparticles with enhanced magnetic properties

Journal of Materials Science & Technology 2023年第30期161卷 161-169页

作者： Chu Shi Jingyi Sheng Guangxiang Si Yan Li Yan Shen Ning Gu Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210009China school of Biomedical Engineering and Informatics Nanjing Medical UniversityNanjing 211166China Medical School Nanjing UniversityNanjing 210093China

Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.

关键词： Iron oxide nanoparticles Spy chemistry Protein immobilization Magnetic resonance imaging Cell labeling

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Protecting People from Tobacco Smoke in China: Current Status and Challenges

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China CDC weekly 2022年第21期4卷 460-464页

作者： Xia Wan Institute of Basic medical Sciences Chinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijingChina

Over the past two years,many people have encountered difficulties because of the advent of coronavirus disease 2019(COVID-19).The COVID-19 pandemic has unleashed many concerns,such as social isolation and loneliness,drastic changes to lifestyles,uncertainty for the future,and financial pressure.Some people reported smoking more than usual to reduce stress or loneliness(1),which made more people vulnerable to be exposed to second-hand tobacco smoke(SHS).As we know there is no safe level of exposure to SHS,and even brief exposure can cause harm(2).Under this circumstance,it is quite meaningful to reiterate the topic of protecting people from the harms of SHS.

关键词： smoke meaningful exposure

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Sonocatalytic hydrogen/hole-combined therapy for anti-biofilm and infected diabetic wound healing

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National Science Review 2023年第5期10卷 262-271页

作者： Qingqing Xu Shengqiang Chen Lingdong Jiang Chao Xia Lingting Zeng Xiaoqing Cai Zhaokui Jin Shucun Qin Wenjiang Ding Qianjun He Taishan Institute for Hydrogen Biomedical Research School of Basic Medical SciencesThe Second Affiliated Hospital of Shandong First Medical University&Shandong Academy of Medical Sciences Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging School of Biomedical EngineeringMedical SchoolShenzhen University Shanghai Key Laboratory of Hydrogen Science&Center of Hydrogen Science School of Materials Science and EngineeringShanghai Jiao Tong University

It is a great challenge to effectively eradicate biofilm and cure biofilm-infected diseases because dense extracellular polymeric substance matrix prevents routine antibacterial agents from penetrating into biofilm.H2is an emerging energy-regulating molecule possessing both high biosafety and high tissue permeability.In this work,we propose a concept of sonocatalytic hydrogen/hole-combined ’inside/outside-cooperation’anti-biofilm for promoting bacteria-infected diabetic wound healing based on two-dimensional piezoelectric nanomaterials.Proof-of-concept experiments using C3N4nanosheets as a representative piezoelectric catalyst with wide band gap and high biosafety have verified that sonocatalytically generated H2and holes rapidly penetrate into biofilm to inhibit bacterial energy metabolism and oxidatively deprive polysaccharides/NADH in biofilm to destroy the bacterial membrane/electron transport chain,respectively,inside/outside-cooperatively eradicating biofilm.A bacteria-infected diabetic wound model is used to confirm the excellent in vivo antibacterial performance of sonocatalytic hydrogen/hole-combined therapy,remarkably improving bacteria-infe cted diabetic wound healing.The proposed strategy of sonocatalytic hole/hydrogen-combined ’inside/outside-cooperation’ will make a highway for treatment of deep-seated biofilm infection.

关键词： nanocatalytic medicine hydrogen therapy biofilm diabetic foot piezoelectric catalysis

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Search for the singlet vector-like top quark in the T→tZ channel with Z→■ at hadron colliders

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Chinese Physics C 2023年第4期 107-115页

作者：韩琳王世钰尚亮亮杨炳方 school of medical Engineering Xinxiang Medical University school of Physics Henan Normal University

Based on a simplified model including a singlet vector-like top quark T with charge |Q|=2/3,we analyze the prospects of observing T via the single T production in the tZ channel with Z decaying to neutrinos at the hadronhadron colliders.This simplified model only includes two free parameters,the coupling constant g*and the T quark mass mT.To investigate the observability of the single T production,we perform a detailed background analysis and detector simulation for the collision energies 14 TeV,27 TeV,and 100 TeV.We scan the g*-mTparameter space and show the exclusion and discovery capabilities on the T quark with the highest integrated luminosity designed at these colliders.Moreover,the limits from the narrow-width approximation and electro weak precision observables are considered.

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Bimetallic Fe-Co Nanoalloy Confined in Porous Carbon Skeleton with Enhanced Peroxidase Mimetic Activity for Multiple Biomarkers Monitoring

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Journal of Analysis and Testing 2023年第1期7卷 53-68页

作者： Jingjing Luo Ruilin Liu Shuchang Zhao Yuan Gao school of Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Carbon-based nanozymes with multifunctional applications have attracted enormous attention,however,there is still a lack of an effective strategy for inexpensive preparation of high-active carbon-based nanozyme.We herein report a waste paperderived CoFe_(2)O_(4)/porous carbon nanozyme for the colorimetric detection of glucose and glutathione(GSH)in biofluids.The hybrid CoFe_(2)O_(4)/porous carbon material was successfully prepared via a combined impregnation,hydrolysis and carbonization method.Newly constructed CoFe_(2)O_(4)/porous carbon material with enhanced peroxidase-like activity could oxidize colorless tetramethylbenzidine(TMB)to blue oxidized TMB with adding H_(2)O_(2).A sensitive colorimetric analysis platform for monitoring the levels of glucose and GSH in biofluids was respectively developed.The proposed analytical method possessed predominant features such as low limit of detections(LODs)(0.16μmol/L for glucose and 120 nmol/L for GSH),broad linear ranges(1-200μmol/L for glucose and 1-50μmol/L for GSH),and excellent practical potential.This multipurpose platform not only provides a promising strategy for transforming waste paper into valuable carbon-based nanozyme,but also paves the way for excavating the potential biomedical and environmental applications from waste paper.

关键词： Carbon nanozyme Fe-Co nanoalloy Glucose Glutathione Colorimetric assay

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The role of cellular and molecular neuroimmune crosstalk in gut immunity

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Cellular & Molecular Immunology 2023年第11期20卷 1259-1269页

作者： Daping Yang Nicole Almanzar Isaac M.Chiu Department of Immunology Harvard Medical SchoolBostonMA02115USA

The gastrointestinal tract is densely innervated by the peripheral nervous system and populated by the immune system.These two systems critically coordinate the sensations of and adaptations to dietary,microbial,and damaging stimuli from the external and internal microenvironment during tissue homeostasis and inflammation.The brain receives and integrates ascending sensory signals from the gut and transduces descending signals back to the gut via autonomic neurons.Neurons regulate intestinal immune responses through the action of local axon reflexes or through neuronal circuits via the gut-brain axis.This neuroimmune crosstalk is critical for gut homeostatic maintenance and disease resolution.In this review,we discuss the roles of distinct types of gut-innervating neurons in the modulation of intestinal mucosal immunity.We will focus on the molecular mechanisms governing how different immune cells respond to neural signals in host defense and inflammation.We also discuss the therapeutic potential of strategies targeting neuroimmune crosstalk for intestinal diseases.

关键词： Neuroimmunology Neuroimmune Host defense Gut Sensory

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Heat stress induced hepatocyte apoptosis in largemouth bass Micropterus salmoides via IRE1α/TRAF2/ASK1/JNK pathway

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Journal of Oceanology and Limnology 2024年第3期42卷 988-1000页

作者： Xuqian ZHAO Wenjia MAO Zijie LIN Qufei LING school of Biology and Basic medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Heat stress(HS)has been shown to adversely affect fish livers and can lead to extensive apoptosis.To investigate the relationship between endoplasmic reticulum(ER)stress and HS-induced apoptosis in fish livers,we isolated and cultured primary hepatocytes of largemouth bass,Micropterus salmoides by trypsin method,then established an in-vitro model of liver cells under HS(35℃).The contents of lactic dehydrogenase(LDH)and hydrogen peroxide(H2O2)were determined to evaluate the effects of HS on hepatocyte injury and oxidative stress.RT-qPCR was performed to discover the key genes in unfolded protein response(UPR)pathways involved at different HS duration.ERS inhibitor 4-PBA and IRE1αinhibitor 4μ8C were used to further investigate the effects of HS on IRE1αapoptosis pathway in hepatocytes.Results show that HS led to significant increases in the release of LDH,the content of H2O2,and the expressions of oxidative protein folding genes(ero1αand pdi)under HS,suggesting severe hepatocyte injury and oxidative stress happened in heat-stressed largemouth bass hepatocytes.The continuous activation of IRE1αpathway genes(grp78,grp94,atf6,perk,eif2a,atf4,chop,ire1α,traf2,ask1,jnk1,and jnk2)indicated that HS led significantly to ER stress.In particular,the mRNA expression levels of ER stress-related genes(grp78,grp94,atf6,perk,ire1α,chop,jnk1,and jnk2)in the high temperature(HT)+4-PBA group and the HT+4μ8C group were significantly down-regulated under HS.After 4μ8C treatment,the expression levels of apoptosis-related genes(caspase-2,caspase-3,caspase-6,caspase-7,caspase-8,caspase-9,and caspase-10)and LDH content were significantly decreased,whereas the cell survival rate was significantly increased when given 4-PBA or 4μ8C treatment.These findings demonstrate that HS could induce liver apoptosis of largemouth bass through the IRE1αpathway,which may act as a key switch mediating liver apoptosis of largemouth bass under HS.

关键词： heat stress Micropterus salmoides endoplasmic reticulum stress apoptosis oxidative stress

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The repression of oncoprotein SET by the tumor suppressor p53 reveals a p53-SET-PP2A feedback loop for cancer therapy

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Science China(Life Sciences) 2023年第1期66卷 81-93页

作者： Han Yao Wenbin Xu Yajing Liu Zhijie Cao Jia Wen Mi Zhang Zhen Wu Xiaojun Yan Zishan Jiao Zijing Zhang Jianyuan Chen Meng Zhang Wei-Guo Zhu Donglai Wang State Key Laboratory of medical Molecular Biology&Department of medical Genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Anatomy Histology and EmbryologySchool of Basic MedicineChina Medical UniversityShenyang 110122China Department of Biochemistry and Molecular Biology Shenzhen University School of MedicineShenzhen 518060China

The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms,including the hijacking of the tumor suppressors p53 and PP2A.Targeting aberrant SET represents a promising strategy for cancer intervention.However,the mechanism by which endogenous SET is regulated in cancer cells remains largely unknown.Here,we identified the tumor suppressor p53 as a key regulator that transcriptionally repressed the expression of SET in both normal and cancer cells.In addition,p53 stimulated PP2A phosphatase activity via p53-mediated transcriptional repression of SET,whereby SET-mediated inhibition of PP2A was alleviated.Moreover,targeting the interaction between SET and PP2A catalytic subunit(PP2Ac)with FTY720 enhanced stress-induced p53 activation via PP2A-mediated dephosphorylation of p53 on threonine 55(Thr55).Therefore,our findings uncovered a previously unknown p53-SETPP2A regulatory feedback loop.To functionally potentiate this feedback loop,we designed a combined therapeutic strategy by simultaneously administrating a p53 activator and SET antagonist in cancer cells and observed a dramatic synergistic effect on tumor suppression.Our study reveals mechanistic insight into the regulation of the oncoprotein SET and raises a potential strategy for cancer therapy by stimulating the p53-SET-PP2A feedback loop.

关键词： p53 SET PP2A FTY720 feedback loop tumor suppression

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肠道病毒在系统性红斑狼疮发病中的作用

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Science Bulletin 2023年第7期68卷 664-665页

作者：李颢 George C.Tsokos Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical SchoolBoston 02215USA

Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by the production of autoantibodies targeting selfantigens and has a complex etiology including both genetic and environmental factors[1].Recently,alterations of the intestinal microbiota have received increasing attention[2]and efforts have begun to correct the dysbiotic environment to treat patients with SLE[3].However,besides bacteria,the microbiome contains other types of organisms including viruses which may infect both host cells and gut bacteria.It is accepted that elements of the microbiome through interactions with intestinal non-lymphoid and lymphoid cells account for the homeostasis of the immune system and the maintenance of gut physiology[4].Due to a series of technical obstacles,including the low representation of virus genomes in microbiome and the paucity of sufficient viral genome sequence database,disease-associated changes of the gut virome in SLE have remained under the radar although viruses have long been considered as one of potent triggers of SLE[5].

关键词：系统性红斑狼疮 alterations 肠道病毒

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Orange-derived extracellular vesicles nanodrugs for efficient treatment of ovarian cancer assisted by transcytosis effect

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5121-5134页

作者： Feng Long Yao Pan Jinheng Li Suinan Sha Xiubo Shi Haoyan Guo Chuanqing Huang Qian Xiao Chao Fan Xingmei Zhang Jun-Bing Fan Ying Wang Cancer Research Institute Experimental Education/Administration CenterKey Laboratory of Functional Proteomics of Guangdong ProvinceSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Neurobiology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate orange-derived extracellular vesicles(OEV)nanodrugs(DN@OEV)by modifying cRGD-targeted doxorubicin(DOX)nanoparticles(DN)onto the surface of OEV,enabling significantly enhancing tumor accumulation and penetration,thereby efficiently inhibiting the growth of ovarian cancer.The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells,which presented the average above 10-fold transcytosis effect compared with individual DN.It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway,thereby inducing the enhanced transcytosis.In particular,the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process.Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of thedrugdelivery system.

关键词： Extracellular vesicles Transcytosis Cancer treatment Drug delivery system Targeted modification Receptor-mediated endocytosis Intracellular trafficking Recycling endosome

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