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Inorganic virus-like nanoparticles for biomedical applications:a minireview

未来食品学报(英文) 2024年第1期4卷 71-82页

作者： Liying Zhao Jiahong Zhou Dawei Deng Department of Pharmaceutical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China

Nature has the ingenious capability to design spiky topological features at the macro-and nanoscales,which exhibits fascinating interface adhesive properties by means of multivalent interactions.Following a biomimetic approach,such as nanoscale virus particles are highly infectious toward host cells,a range of organic and inorganic spiky particles(virus-like nanostructures)have been precisely engineered for diverse biomedical applications.Generally,organic virus-like particles(VLPs)derived from viral capsids(often termed as virosomes)have been extensively studied and reviewed,but concomitant concerns regarding immunogenicity and risks of mutagenesis limit clinical potential of organic VLPs.In contrast,inorganic VLPs(viral-mimicking topography)possess fascinating physicochemical characteristics,such as excellent electrical,optical,magnetic,mechanical and catalytic properties,which make them particularly suitable for biomedical applications.Alternatively,there is no comprehensive review related to inorganic VLPs engineered with non-viral shell for biomedical applications.Hence,in this review,we present a brief overview on inorganic VLPs,followed by summarizing the construction and properties of virus-like nanostructures,as well as the mechanisms of nano-bio interface interactions initiated by spiky topography.Furthermore,we focus on the recent advances of VLPs for biomedical applications(including biosensing,antibacterial therapy and cancer treatment).Finally,the future outlook and emerging challenges will be presented.This review aims to provide future scope of the rational design of inorganic non-viral vectors,especially with respect to gene-based therapy platforms.

关键词： Nanotopography Virus-like spike Inorganic particles Biomedical applications

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Cytological and molecular characteristics of delayed spike development in wheat under low temperature in early spring

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The Crop Journal 2022年第3期10卷 840-852页

作者： Xurun Yu Yufei Jiang Huihui Yao Liping Ran Yong Zang Fei Xiong Jiangsu Key Laboratory of Crop Genetics and Physiology/Jiangsu Key Laboratory of Crop Cultivation and Physiology Agricultural College of Yangzhou UniversityCo-Innovation Center for Modern Production Technology of Grain CropsYangzhou UniversityYangzhou 225009JiangsuChina Yangzhou University Guangling College Yangzhou 225000JiangsuChina

Low temperature in early spring impairs wheat growth and grain yield.However,little is known about the cytological and molecular mechanisms underlying low temperature regulation of wheat spike development.Microstructure observation and transcriptome sequencing of wheat spikes under low temperature were conducted.Low temperature slowed spike development,reduced the yield-component parameters of wheat spikes at the harvest stage,delayed the formation of lateral spikelets and tissue development,and induced the early differentiation of terminal spikelets.Low temperature increased the content of abscisic acid and caused the upregulation of genes in the abscisic acid signaling pathway,including those encoding PP2 Cs,Sn RK2 s,and b ZIP transcription factors.Low temperature also induced the upregulation of 33 cold-responsive genes involved in wheat response to low-temperature stress and regulation of abscisic acid biosynthesis and metabolism of other substances.The wheat spike adapted to cold conditions by changing the expression levels of genes involved in spike morphogenesis,including the transcription-factor genes MADS6,ERF4,ERF78,WOX6,and NAC48.These findings suggest that low temperature in early spring delays wheat spike development by increasing abscisic acid content or affecting the expression of genes involved in morphogenesis.

关键词： Development Low temperature spike Transcriptome Wheat

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TMPRSS2 and SARS-CoV-2 spike interaction assay for uHTS

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Journal of Molecular Cell Biology 2023年第3期15卷 32-43页

作者： Danielle Cicka Qiankun Niu Min Qui Kun Qian Eric Miller Dacheng Fan Xiulei Mo Andrey AIvanov Stefan GSarafianos Yuhong Du Haian Fu Department of Pharmacology and Chemical Biology Emory University School of MedicineAtlantaGA 30322USA Graduate Program in Molecular and Systems Pharmacology Laney Graduate School of Emory UniversityAtlantaGA 30322USA Emory Chemical Biology Discovery Center Emory University School of MedicineAtlantaGA 30322USA Winship Cancer Institute of Emory University AtlantaGA 30322USA Laboratory of Biochemical Pharmacology Department of PediatricsEmory University School of MedicineAtlantaGA 30322USA

SARS-CoV-2,the coronavirus that causes the disease COVID-19,has claimed millions of lives over the past 2 years.This demands rapid development of effective therapeutic agents that target various phases of the viral replication cycle.The interaction between host transmembrane serine protease 2(TMPRSS2)and viral spike protein is an important initial step in SARS-CoV-2 infection,offering an opportunity for therapeutic development of viral entry inhibitors.Here,we report the development of a time-resolved fluorescence/Förster resonance energy transfer(TR-FRET)assay for monitoring the TMPRSS2–spike interaction in lysate from cells co-expressing these proteins.The assay was configured in a 384-well-plate format for high-throughput screening with robust assay performance.To enable large-scale compound screening,we further miniaturized the assay into 1536-well ultrahigh-throughput screening(uHTS)format.A pilot screen demonstrated the utilization of the assay for uHTS.Our optimized TR-FRET uHTS assay provides an enabling platform for expanded screening campaigns to discover new classes of small-molecule inhibitors that target the spike and TMPRSS2 protein–protein interaction.

关键词： SARS-CoV-2 COVID-19 protein-protein interaction TMPRSS2 spike high-throughput screening TR-FRET

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Systematic evaluation of IgG responses to SARS-CoV-2 spike protein-derived peptides for monitoring COVID-19 patients

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Cellular & Molecular Immunology 2021年第3期18卷 621-631页

作者： Yang Li Dan-yun La Qing Lei Zhao-wei Xu Feng Wang Hongyan Hou Lingyun Chen Jiaoxiang Wu Yan Ren Ming-liang Ma Bo Zhang Hong Chen Caizheng Yu Jun-biao Xue Yun-xiao Zheng Xue-ning Wang He-wei Jiang Hai-nan Zhang Huan Qi Shu-juan Guo Yandi Zhang Xiaosong Lin Zongjie Yao Pengfei Pang Dawei Shi Wei Wang Xiao Yang Jie Zhou Huiming Sheng Ziyong Sun Hong Shan Xionglin Fan Sheng-ce Tao Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine(Ministry of Education)Shanghai Jiao Tong UniversityShanghaiChina Department of Pathogen Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Key Laboratory of Gastrointestinal Cancer(Fujian Medical University) Ministry of EducationSchool of Basic Medical SciencesFujian Medical UniversityFuzhouChina Department of Clinical Laboratory Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina SBGI Education Center University of Chinese Academy of SciencesShenzhen 518083China Tongren Hospital Shanghai Jiao Tong University School of MedicineShanghaiChina BGI-Shenzhenf Shenzhen 518083 China Department of Public Health Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Center for Interventional Medicine The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China National Institutes for Food and Drug Control Beijing 100050China Foshan Fourth Peopled Hospital Foshan 528000China Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

Serological tests play an essential role in monitoring and combating the COVID-19 pandemic.Recombinant spike protein(S protein),especially the S1 protein,is one of the major reagents used for serological tests.However,the high cost of S protein production and possible cross-reactivity with other human coronaviruses pose unavoidable challenges.By taking advantage of a peptide microarray with full spike protein coverage,we analyzed 2,434 sera from 858 COVID-19 patients,63 asymptomatic patients and 610 controls collected from multiple clinical centers.Based on the results,we identified several S protein-derived 12-mer peptides that have high diagnostic performance.In particular,for monitoring the IgG response,one peptide(aa 1148-1159 or S2-78)exhibited a sensitivity(95.5%,95%CI 93.7-96.9%)and specificity(96.7%,95%CI 94.8-98.0%)comparable to those of the S1 protein for the detection of both symptomatic and asymptomatic COVID-19 cases.Furthermore,the diagnostic performance of the S2-78(aa 1148-1159)IgG was successfully validated by ELISA in an independent sample cohort.A panel of four peptides,S1-93(aa 553-564),S1-97(aa 577-588),S1-101(aa 601-612)and S1-105(aa 625-636),that likely will avoid potential cross-reactivity with sera from patients infected by other coronaviruses was constructed.The peptides identified in this study may be applied independently or in combination with the S1 protein for accurate,affordable,and accessible COVID-19 diagnosis.

关键词： SARS-CoV-2 spike peptide Antibody Diagnosis

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A low-pass filter of 300 Hz improved the detection of pacemaker spike on remote and bedside electrocardiogram

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Chinese Medical Journal 2019年第5期132卷 534-541页

作者： Jian Sun Qiu-Feng Lu Yan Zhao Peng-Pai Zhang Jun Wang Qun-Shan Wang Xiao-Hong Liu Yi-Gang Li Department of Cardiology Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200092 China

Background: The current upper-frequency cutoff of 150Hz sometimes causes loss of pacemaker spike and misdiagnosis, hypothesized that low-pass filter (LPF) other than 150Hz could improve the detection of pacemaker spike. This study aimed to examine the effect of different LPF on pacemaker spike detection in remote and bedside electrocardiogram (ECG). Methods: Patients with permanent pacemaker implantation were included during routine follow-up. Standard 12-lead ECGs at 6 different upper-frequency cutoff (40,100,150,200, 300, and 400 Hz) were collected. All ECGs were then transmitted to the remote clinic center. Ventricular and atrial pacing were analyzed by 2 independent medical practitioners. Results: A total of 88 patients5 ECGs were analyzed (mean age 73.8±10.2 years and 85 with dual-chamber pacemakers). About 75.3%(64/85) of patients were diagnosed as atrial pacing by pacemaker programming. Among 6 different upper-frequency cutoff, the 300 Hz turned out to perform best in detecting atrial-paced spike (area under the curve [AUC]=0.73, 95% confidence interval [CI]:0.61-0.84 vs.0.56, 95% CI: 0.61-0.84 at 150 Hz;P=0.002) on bedside ECGs. Using programming as the golden standard, the 300 Hz LPF has a sensitivity of 59.4%, specificity of 85.7%, positive predictive value of 92.7% and negative predictive value of 40.9% on bedside ECGs. As for the ventricular pacing, the 300Hz LPF also had a higher accuracy (AUC=0.93;95% CI = 0.84-1.00) than that at 150Hz (AUC = 0.86;95% CI:0.77-0.94;Pspike on bedside ECGs. The results of remote ECGs were similar with bedside ECGs. Conclusions: A filter of 300 Hz cutoff may be recommended for ECG spike detection. With the recommended parameter, remote ECG can perform as well as bedside ECG.

关键词： Digital electrocardiogram Pacemaker spike Upper-frequency cutoff Remote electrocardiogram

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Evaluation of purified recombinant spike fragments forassessment of the presence of serum neutralizing antibodiesagainst a variant strain of porcine epidemic diarrhea virus

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Virologica Sinica 2017年第4期32卷 307-316页

作者： Jianwei Hao Yun Zhang Shengkun Fang Zhifen Wen Xiangbin Zhang Chunyi Xue Yongchang Cao State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen UniversityGuangzhou510006China Fraunhofer-lnstitut for Angewandte Informationstechnik FIT Sankt Augustin 53754Germany

Since 2010, variant strains of porcine epidemic diarrhea virus(PEDV) have caused disasters in the pork industry. The spike(S) protein, as the major immunity-eliciting antigen, has previously been used for serological testing and has been found to correlate significantly with the results of the serum neutralization(SN) test. However, further evaluation of this method is needed as new epidemic strains of PEDV emerge. Hence, the main objective of this study was to assess sow sera and determine the correlation between enzyme-linked immunosorbent assay(ELISA) results(involving a newly isolated GDS01 virus-based ELISA and ELISAs based on seven recombinant fragments comprising overlapping S1 and partial S2 sequences) and SN titers. Furthermore, we determined the reliability of the ELISAs based on receiver operating characteristics(ROC) curve analyses. For the most promising ELISA, i.e., the SP4 ELISA, the correlation coefficient(r) and the area under curve(AUC) were determined to be 0.6113 and 0.8538, respectively. In addition, we analyzed the homology of the SP4 sequences obtained from different strains(including vaccine strains) and found that various strains showed a high degree of homology in this region. Thus, we conclude that SP4 is a promising serological testing protein for use in the field.

关键词： Porcine epidemic diarrhea virus (PEDV) spike protein enzyme-linkedimmunosorbent assay serum neutralization test

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Evolution of the ring-like vortices and spike structure in transitional boundary layers

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Science China(Physics,Mechanics & Astronomy) 2010年第3期53卷 514-520页

作者： OLIVEIRA Maria Department of Mathematics University of Texas at Arlington Arlington Texas 76010 USA

At the late stage of transitional boundary layers, the nonlinear evolution of the ring-like vortices and spike structures and their effects on the surrounding flow were studied by means of direct numerical simulation with high order accuracy. A spatial transition of the flat-plate boundary layers in the compressible flow was conducted. Detailed numerical results with high resolution clearly represented the typical vortex structures, such as ring-like vortices and so on, and induced ejection and sweep events. It was verified that the formation of spike structures in transitional boundary layers had close relationship with ring-like vortices. Especially, compared to the newly observed positive spike structure in the experiments, the same structure was found in the present numerical simulations, and the mechanism was also studied and analyzed.

关键词： boundary layer transition ring-like vortices spike structure direct numerical simulation

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The spike weight contribution of the photosynthetic area above the upper internode in a winter wheat under different nitrogen and mulching regimes

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The Crop Journal 2019年第1期7卷 89-100页

作者： Wei Chen Jingjuan Zhang Xiping Deng Key Laboratory of Disaster Monitoring and Mechanism Simulating of Shaanxi Province Baoji University of Arts and Sciences State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau Institute of Soil and Water Conservation Northwest A&F University and Chinese Academy of Sciences School of Veterinary and Life Sciences Murdoch University

Besides leaves, non-foliar green organs such as stem and spike are also considered photosynthetic organs. To assess the photosynthetic contributions of these organs, the correlations between these photosynthetic areas and single-spike weight were investigated in a winter wheat(Triticum aestivum L.) under four nitrogen and mulching treatments: N120,N150, N195, and N195 + M. Two-year repeated field experiments were conducted on the Loess Plateau of China. Non-foliar photosynthetic area, grain-filling ratio and duration,grain yield, and in particular, single-spike weight, were measured, recorded and analyzed.Under the N195 + M treatment, plants showed the largest area of photosynthetic organs(flag leaf and non-foliar organs) and the highest grain yield and single spike weight. Singlespike weight was positively correlated with the areas of all examined non-foliar photosynthetic organs, in particular with the area above the flag leaf node(R^2= 0.761*)and the area above the exposed part of the peduncle(EXP)(R^2= 0.800**). In addition, singlespike weight was highly correlated with average grain-filling ratio(R^2= 0.993**), whereas it was less highly correlated with grain-filling duration(R^2= 0.533). The morphological traits of non-foliar photosynthetic organs were also more highly correlated with average grainfilling ratio than with average grain-filling duration. The significant correlation between each of the morphological traits(area, length and width) of EXP and single-spike weight indicates that morphological traits of EXP are important in determining spike weight in the Loess Plateau environment.

关键词： Grain-filling ratio Grain-filling duration Loess Plateau Photosynthetic organs Single spike weight Winter wheat

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Enhancement of spike coherence by the departure from Gaussian noise in a Hodgkin-Huxley neuron

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Science China Chemistry 2009年第8期52卷 1186-1191页

作者： XIE YanHang GONG YuBing HAO YingHang School of Physics&Electronic Engineering Ludong UniversityYantai 264025China

Experimental study has shown that non-Gaussian noise exists in sensory systems like neurons.The departure from Gaussian behavior is a characteristic parameter of non-Gaussian noise.In this paper,we have numerically studied the effect of a particular kind of non-Gaussian colored noise(NGN),especially its departure q from Gaussian noise(q = 1),on the spiking activity in a deterministic Hodgkin-Huxley(HH) neuron driven by sub-threshold periodic stimulus.Simulation results show that the departure q can affect the spiking activity induced by noise intensity D.For smaller q values,the minimum in the variation coefficient(CV) as a function of noise intensity(D) becomes smaller,showing that D-induced stochastic resonance(SR) becomes strengthened.Meanwhile,depending on the value of D,q can either enhance or reduce the spiking regularity.Interestingly,CV changes non-monotonously with varying q and passes through a minimum at an intermediate q,representing the presence of "departure-induced SR".This result shows that appropriate departures of the NGN can enhance the spike coherence in the HH neuron.Since the departure of the NGN determines the probability distribution and hence may denote the type of the noise,"departure-induced SR" shows that different types of noise can enhance the spike coherence,and hence may improve the timing precision of sub-threshold signal encoding in the HH neuron.

关键词： neuron non-Gaussian colored noise spike coherence stochastic resonance stochastic dynamics

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Modeling the spike Response for Adaptive Fuzzy Spiking Neurons with Application to a Fuzzy XOR

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Computer Modeling in Engineering & Sciences 2018年第6期115卷 295-311页

作者： A.M.E.Ramírez-Mendoza CONACYT Research Fellow–State University of Nuevo León(UANL for its acronym in Spanish) Mechanical and Electrical Engineering School(FIME for its acronym in Spanish)Center for Research and Innovation in Aeronautical Engineering(CIIIA for its acronym in Spanish)Carretera a Salinas Victoria km.2.3ApodacaNuevo LeónMéxico

A spike response model(SRM)based on the spikes generator circuit(SGC)of adaptive fuzzy spiking neurons(AFSNs)is developed.The SRM is simulated in MatlabTM environment.The proposed model is applied to a configuration of a fuzzy exclusive or(fuzzy XOR)operator,as an illustrative example.A description of the comparison of AFSNs with other similar methods is given.The novel method of the AFSNs is used to determine the value of the weights or parameters of the fuzzy XOR,first with dynamic weights or self-tuning parameters that adapt continuously,then with fixed weights obtained after training,finally with fixed weights and a dynamic gain or self-tuning gain for a fine adjustment of amplitude.

关键词： spike response model spikes generator circuit fuzzy XOR adaptive fuzzy spiking neuron learning algorithm fuzzy neuron self-tuning

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