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Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation

Chemical Research in Chinese Universities 2017年第3期33卷 392-399页

作者： PAN Dong WANG Lincong LIU Meiyi JIN Shi WANG Liyan YU Xianghui ZHA Xiao WU Yuqing state Key laboratory of Supramoleeular Structure and Materials College of Computer Science and Technology Institute of Theoretical Chemistry state engineering laboratory of aids vaccine Jilin University Changehun 130012 P. R. China Sichuan Cancer Hospital & Institute Chengdu 610041 P. R. China

Located at the carboxyl terminal of the human papillomavirus major capsid protein L1, helix-5（h5） is cru-cial to L1 folding and pentamer formation. Site-directed mutagenesis of the leucine residue on site 469 into lysine, alanine, serine and glycine was performed to explore the effect of the resultant mutations on L 1 pentamer formation. The soluble yields of the L1 pentamers of the L469A and L469K mutants were nearly two fold higher than that of the wild type. Molecular dynamics simulation was then performed to reveal the intrinsic mechanisms involved in the improvement of L 1 pentamer yield. Accordingly, the secondary structures of h5, β-G2, β-B1, β-C, β-D, and β-F were altered. The altered structures improved the hydrophobic interaction between h5 and fl-core ＂jelly＂ and the stability of h5. The hydrophobic surface area of residue 469 was reduced by 50% relative to that of the wild type. The C--O group of residue 469 and C--N group of L470 were both exposed to the solvent in the L469A mutant. These modifications may account for the increased solubility and stability and the promotion of pentamer formation induced by the point mutation. Therefore, the changes in the hydrophobic properties of h5 and the core structure determined the pentamer formation and solubility. This study may assist the development of a cost-effective platform for the production of prophylactic virus-like particle vaccines.

关键词： Human papillomavirus Capsid protein Helix-5 L1 pentamer

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Functionalization of Magnetic Titanium Dioxide for Targeted Drug Delivery and UV-induced Release

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Chemical Research in Chinese Universities 2017年第2期33卷 294-297页

作者： CAI Linjun LI Junbo WANG Shipeng ZHAO Mengzhe ZHAO Bing JIANG Chunlai KONG Wei National engineering laboratory for aids vaccine College of Life Sciences Jilin University Changchun 130012 P. R. China state Key laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun 130012 R R. China

Magnetic titanium dioxide core-shell nanoparticles（Fe3O4@TiO2 NPs） were synthesized as particles withappropriate size for intravenous injection. They subsequently were functionalized with p-aminothiophenol（PATP） tofacilitate the covalent attachment of target drugs through azo coupling reaction, which can be universally observed ina variety of drugs containing phenols, anilines, and imidazoles. The proposed drug nanocarrier was designed to po-ssess the ability to release drugs upon UV irradiation because of the photocatalytic property of the TiO2 shells. All theresults indicate the potential application of the Fe3O4@TiO2 NPs in targeted drug delivery with greater chemical sta-bility and universality.

关键词： Magnetic titanium dioxide Targeted drug delivery Azo coupling

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Robust neutralization of SARS-CoV-2 variants including JN.1 and BA.2.87.1 by trivalent XBB vaccine-induced antibodies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2359-2361页

作者： Xun Wang Shujun Jiang Wentai Ma Yanliang Zhang Pengfei Wang Shanghai Pudong Hospital Fudan University Pudong Medical CenterState Key Laboratory of Genetic EngineeringMOE Engineering Research Center of Gene TechnologySchool of Life SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghaiChina Department of Infectious Diseases Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing Research Center for Infectious Diseases of Integrated Traditional Chinese and Western MedicineNanjingJiangsuChina Beijing Institute of Genomics Chinese Academy of SciencesUniversity of Chinese Academy of Sciences and China National Center for BioinformationBeijingChina

Dear Editor,The rapid and widespread transmission of SARS-CoV-2 has led to the emergence of multiple variants of concern(VOCs),most notably the Omicron variant,which continues to evolve and diversify into a range of *** previous research has shown that these Omicron sub-lineages,spanning BA.1-BA.2.86,have been evolving to exhibit increased neutralization escape capabilities.

关键词： evolve neutralization variants

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A Novel Eccentric Intrusion Detection Model Based on Recurrent Neural Networks with Leveraging LSTM

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Computers, Materials & Continua 2024年第3期78卷 3089-3127页

作者： Navaneetha Krishnan Muthunambu Senthil Prabakaran Balasubramanian Prabhu Kavin Kishore Senthil Siruvangur Kavitha Chinnadurai Jehad Ali Department of Computer Applications Karpagam College of EngineeringCoimbatore641032India Department of Computer Science and engineering Karpagam College of EngineeringCoimbatore641032India Department of Data Science and Business Systems College of Engineering and TechnologySRM Institute of Science and TechnologyKattankulathur603203India Department of Computer Science and engineering Sathyabama Institute of Science and TechnologyJeppiaar NagarRajiv Gandhi SalaiChennai600119India Department of AI Convergence Network Ajou UniversitySuwon16499Korea

The extensive utilization of the Internet in everyday life can be attributed to the substantial accessibility of online services and the growing significance of the data transmitted via the ***,this development has expanded the potential targets that hackers might *** adequate safeguards,data transmitted on the internet is significantly more susceptible to unauthorized access,theft,or *** identification of unauthorised access attempts is a critical component of cybersecurity as it aids in the detection and prevention of malicious *** research paper introduces a novel intrusion detection framework that utilizes Recurrent Neural Networks(RNN)integrated with Long Short-Term Memory(LSTM)*** proposed model can identify various types of cyberattacks,including conventional and distinctive *** networks,a specific kind of feedforward neural networks,possess an intrinsic memory *** Neural Networks(RNNs)incorporating Long Short-Term Memory(LSTM)mechanisms have demonstrated greater capabilities in retaining and utilizing data dependencies over extended *** such as data types,training duration,accuracy,number of false positives,and number of false negatives are among the parameters employed to assess the effectiveness of these models in identifying both common and unusual *** are utilised in conjunction with LSTM to support human analysts in identifying possible intrusion events,hence enhancing their decision-making capabilities.A potential solution to address the limitations of Shallow learning is the introduction of the Eccentric Intrusion Detection *** model utilises Recurrent Neural Networks,specifically exploiting LSTM *** proposed model achieves detection accuracy(99.5%),generalisation(99%),and false-positive rate(0.72%),the parameters findings reveal that it is superior to state-of-the-art techniques.

关键词： Cybersecurity intrusion detection machine learning leveraging long short-term memory(LLSTM) CICIDS2019 dataset innovative cyberattacks

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Immunological and virological characteristics of human immunodeficiency virus type i superinfection： implications in vaccine design

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Frontiers of Medicine 2017年第4期11卷 480-489页

作者： Yang Gao Wen Tian Xiaoxu Han Feng Gao Key laboratory of aids Immunology of Nattonal Health and Famdy Plannmg Commtsston Department of Laboratory Medicme The First Affiliated Hospital China Medical University Shenyang 110001 China National engineering laboratory for aids vaccine School of Life Sciences Jilin University Changehun 130012 China Department of Medicine Duke University Medical Center Durham NC 27710 USA

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I （HIV-1）. Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

关键词： human immunodeficiency virus type I superinfection incidence immtme response

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Facile Preparation and Cellular Imaging of Photoluminescent Carbogenic Nanoparticles Derived from Defoliations

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Chemical Research in Chinese Universities 2013年第1期29卷 189-192页

作者： XIU Yang ZHOU Yan GAO Qian CHEN Jie-sheng LI Guo-dong state Key laboratory of Inorganic Synthesis and Preparative Chemistry College of Chemistry National engineering laboratory for aids vaccine College of Life Science Jilin University Changchun 130012 P. R. China" School of Chemistry and Chemical engineering Shanghai Jiao Tong University Shanghai 200240 P. R. China

In the past two decades, photoluminescent semiconductor quantum dots（QDs） have received intensive attention for a variety of promising properties and applications, especially for their potential application in cellular imagingE. QDs with high quantum yield have been prepared based on cad mium（zinc） selenide（sulfide） and related coreshell compo sites. However, the release of Cd2＋, S2 and Se2 ions in evitably causes serious health and environmental concerns. Therefore, many efforts have been devoted to developing be nign alternatives with enhanced photoluminescence, such as silicon nanoparticles and nanowires. Carbonbased nanomaterials, including carbon nano tubes（CNTs） and carbogenic nanoparticles（CNPs）, represent an exciting new type of alternative to the aforementioned QDs with high quantum yield. CNPs are superior to QDs in chemi cally inertness, biocompatibility and photostability. After the report on the photoluminescence of carbon dots prepared by laser ablation with graphite as carbon sourcetill, several strate gies have been developed for the preparation of luminescent CNPs. For instance, luminescent CNPs were prepared by Liu et al.021 with candle soot via oxidative acid treatment, and the resulting CNPs with different emission colors were isolated by means of electrophoretic separation. Hu et al. employed an improved onestep approach for the synthesis of luminescent CNPs by laser irradiating a suspension of carbon materials in organic solvents of diamineterminated oligomeric poly（ethylene glycol）（PEG1500N）. More recently, luminescent carbogenic dots have been obtained by Peng and Travas via surface passivation of carbogenic dots in an aqueous solution with carbohydrates as the starting materials. Carbogenic nano particlesloaded magnesiumaluminophosphate solid phosphors.

关键词： Carbogenic nanoparticle Photoluminescence Cellular imaging

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Choosing Multimodal Freight Mix: An Integrated Multi-Objective Multicriteria Approach

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Journal of Transportation Technologies 2024年第3期14卷 402-422页

作者： Mohammad Anwar Rahman School of engineering Science & Technology Central Connecticut State University New Britain CT USA

Multimodal freight transportation emerges as the go-to strategy for cost-effectively and sustainably moving goods over long distances. In a multimodal freight system, where a single contract includes various transportation methods, businesses aiming for economic success must make well-informed decisions about which modes of transport to use. These decisions prioritize secure deliveries, competitive cost advantages, and the minimization of environmental footprints associated with transportation-related pollution. Within the dynamic landscape of logistics innovation, various multicriteria decision-making (MCDM) approaches empower businesses to evaluate freight transport options thoroughly. In this study, we utilize a case study to demonstrate the application of the Technique for Order Preference by Similarity to the Ideal Solution (TOPSIS) algorithm for MCDM decision-making in freight mode selection. We further enhance the TOPSIS framework by integrating the entropy weight coefficient method. This enhancement aids in assigning precise weights to each criterion involved in mode selection, leading to a more reliable decision-making process. The proposed model provides cost-effective and timely deliveries, minimizing environmental footprint and meeting consumers’ needs. Our findings reveal that freight carbon footprint is the primary concern, followed by freight cost, time sensitivity, and service reliability. The study identifies the combination of Rail/Truck as the ideal mode of transport and containers in flat cars (COFC) as the next best option for the selected case. The proposed algorithm, incorporating the enhanced TOPSIS framework, benefits companies navigating the complexities of multimodal transport. It empowers making more strategic and informed transportation decisions. This demonstration will be increasingly valuable as companies navigate the ever-growing trade within the global supply chains.

关键词： Multimodal Freight Transport MCDM TOPSIS Entropy Technique COFC

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Objective Evaluation Method of Steering Comfort Based on Movement Quality Evaluation of Driver Steering Maneuver

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Chinese Journal of Mechanical engineering 2014年第5期27卷 1027-1037页

作者： YANG Yiyong LIU Yahui WANG Man JI Run JI Xuewu School of engineering and Technology China University of Geosciences(Beijing) state Key laboratory of Automotive Safety and Energy Tsinghua University National Research Center for Rehabilitation Technical aids

The existing research of steering comfort mainly focuses on the subjective evaluation,aiming at designing and optimizing the steering *** the development of steering system,especially the evaluation of steering comfort,the objective evaluation methods considered the kinematic characteristics of driver steering maneuver are not proposed,which means that the objective evaluation of steering cannot be conducted with the evaluation of kinematic characteristics of driver in steering *** order to propose the objective evaluation methods of steering comfort,the evaluation of steering movement quality of driver is developed on the basis of the study of the kinematic characteristics of steering ***,the steering motion trajectories of the driver in both comfortable and certain extreme uncomfortable operation conditions are detected using the Vicon motion capture *** operation conditions are under the restrictions of the vertical height and horizontal distance between steering wheel center and the H-point of driver,and the steering resisting torque ***,the movement quality evaluation of driver steering maneuver is assessed using twelve kinds of evaluation indices based on the kinematic analyses of the steering motion trajectories to propose an objective evaluation ***,an integrated discomfort index of steering maneuver is proposed on the basis of the regression analysis of subjective evaluation rating and the movement quality evaluation indices,including the Jerk,Discomfort and Joint Torque *** test results show that the proposed integrated discomfort index gives a good fitting with the subjective evaluation of discomfort,which means it can be used to evaluate or predict the discomfort level of steering *** paper proposes an objective evaluation method of steering comfort based on the movement quality evaluation of driver steering maneuver.

关键词： steering maneuver movement quality evaluation driver discomfort

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Role of helicity of a-helical antimicrobia peptides to improve specificity

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Protein & Cell 2014年第8期5卷 631-642页

作者： Yibing Huang Liyan He Guirong Li Naicui Zhai Hongyu Jiang Yuxin Chen Key laboratory for Molecular Enzymology and engineering of the Ministry of Education Jilin University Changchun 130012 China National engineering laboratory for aids vaccine Jilin University Changchun 130012 China School of Life Sciences Jilin University Changchun 130012 China The First Hospital Jilin University Changchun 130021 China

A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic a-helical antimicrobial peptide A12L/A20L （Ac-KWKSFLKTFKSLK KTVLHTLLKAISS-amide） was used as the framework to design a series of D- and L-diastereomeric peptides and study the relationships of helicity and biological activi- ties of o-helical antimicrobial peptides. Peptide helicity was measured by circular dichroism spectroscopy and demonstrated to correlate with the hydrophobicity of peptides and the numbers of D-amino acid substitu- tions. Therapeutic index was used to evaluate the selectivity of peptides against prokaryotic cells. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, the hemolytic activity of peptide analogs have been significantly reduced. Compared to the parent peptide, the therapeutic indices were improved of 44-fold and 22-fold against Gram-negative and Gram- positive bacteria, respectively. In addition, D- and L-diastereomeric peptides exhibited lower interaction with zwitterionic eukaryotic membrane and showed the significant membrane damaging effect to bacterial cells. Helicity was proved to play a crucial role on peptide specificity and biological activities. By simply replacing the hydrophobic or the hydrophilic amino acid residues on the non-polar or the polar face of these amphipathic derivatives of the parent peptide with D-amino acids, we demonstrated that this method could have excellent potential for the rational design of antimicrobial pep- tides with enhanced specificity.

关键词： antimicrobial peptides (AMPs) peptideantibiotics helicity secondary structure diastereomericpeptides specificity therapeutic index

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Identification of Cinobufagin and Resibufogenin as Inhibitors of Enterovirus 71 Infection

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Chemical Research in Chinese Universities 2014年第6期30卷 953-958页

作者： CHEN Jiawen XU Lin SUN Shiyang ZHANG Huafei MA Tonghui SU Weiheng JIANG Chunlai National engineering laboratory for aids vaccine Key laboratory for Molecular Enzymology & engineering Ministry of Education School of Life Seiences Jilin University Changchun 130012 P. R. China" College of Basic Medical Sciences Dalian Medical University Dalian 116044 t~ R. China

In this paper, cinobufagin and resibufogenin were found to inhibit enterovirus 71（EV71） infection in vitro in cell viability and plaque reduction assays. The 50% inhibitory concentrations（lCs0） of einobufagin and resibufoge- nin were （10.94±2.36） and （218±31） nmol/L, respectively, the 50% cytotoxic concentrations（CCs0） of them were （1277±223） and （1385±254） nmol/L, respectively, and the anti-EV71 selectivity index（SI50） of cinobufagin was 116.7, which are promisingly developed into drug. Using a VP1 detection assay and a constructed reporter luciferase, we found that cinobufagin and resibufogenin disrupted the synthesis of EV71 protein. However, neither of them inhibited EV71 RNA replication. Our study suggests that cinobufagin and resibufogenin are the promising candidates that should he fllrther investigated for the treatment of EV71 caused disease.

关键词： Enterovirus 71 Coxsackievirus A16 Cinobufagin Resibufogenin Chansu

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