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Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing

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Acta Pharmaceutica Sinica B 2023年第2期13卷 852-862页

作者： Xiaolin Zhang xueyan zhen Yixuan Yang Quan Feng Wanqing Yuan Xiaoyu Xie School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an 710061China Shaanxi Engineering Research Center of Cardiovascular Drugs Screening&Analysis Xi'an 710061China

Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting ***,random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites,especially when applied to intracellular regions of transmembrane *** reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living ***,inside-out cell membrane camouflaged magnetic nanoparticles(IOCMMNPs)were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor *** functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe_(3)O_(4)nanoparticles to prepare *** inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification ***,two compounds,senkyunolide A and ligustilidel,were successfully captured,and their potential antiproliferative activities were further testified by pharmacological *** is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

关键词： Cell membrane camouflaged nanoparticles Inside-out cell membrane coating Bioorthogonal reactions Drug leads discovery Traditional Chinese medicine Magnetic nanoparticles Precise assembly Alkynyl functionalization

Song Ci,A Medicolegist

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Journal of Traditional Chinese Medical Sciences 2021年第4期8卷 265-266页

作者： Yinghua Huang xueyan zhen Yongxuan Liang Beijing University of Chinese Medicine Beijing102488China

Song Ci(courtesy name:Song Huifu,1186e1249),a famous medicolegist of the Southern Song Dynasty(1127e1279)was from Jianyang,present Nanping,Fujiang *** Yuan Ji Lu(The Record For Vindication)written by him is the first and extant monography on forensic medicine in the world,for which Song was honored as the founder of forensic *** was born into an official *** father once served as the governor of Guangzhou,so he received good education since *** ten year old,he studied with one of the pupils of Zhu Xi(1130e1200),the authority of the neo-confucianism in the Song Dynasty and other great scholars.

关键词： Province. education

Biointerface engineering of self-protective bionic nanomissiles for targeted synergistic chemotherapy

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Chinese Chemical Letters 2023年第4期34卷 116-121页

作者： xueyan zhen Linhao Li Lanlan Jia Aihong Zhu Yixuan Yang Sicen Wang Xiaoyu Xie School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China Shaanxi Engineering Research Center of Cardiovascular Drugs Screening&Analysis Xi’an 710061China

Erythrocyte membrane(EM)-camouflaged chemotherapeutic delivery nanovehicles hold promise for solid tumor therapy because of their excellent biostability and biocompatibility. However, it is accompanied with insufficient targeting effect and deficient pharmacokinetic behavior due to the lack of a regulated biointerface to navigate and overcome biological transportation obstacles in solid tumor ***, an anti-epidermal growth factor receptor(EGFR) aptamer(EApt) modified and EM-cloaked chemotherapeutic nanomissile delivery system was constructed. The anchored-EApt acting as a specific EGFR suppressor promotes to inhibit the overexpression of EGFR and initiate the cell apoptosis. Importantly, the resulting PLGA-DOX@EM-EApt orchestrated the bioactivity of each component and provided synergistic cell apoptosis and antitumor effects by precisely suppressing EGFR expression levels and delivering DOX. The in vitro and in vivo experimental results confirmed that the immune escape and active targeting behaviors of PLGA-DOX@EM-EApt could significantly promote its drug retention and tumor inhibition abilities. Our findings propose a novel strategy using the biointerface functionalization technique, demonstrating a promising therapeutic platform via a biomimetic drug delivery system for precise solid tumor recognition and synergistic therapy.

关键词： Aptamer Self-protective Biointerface Targeted drug delivery Synergistic chemotherapy

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang zhen Qiu Shangxiu Chen Yuhan Huang zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological ***,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains ***,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH *** the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH *** of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)***’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 *** findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

Neural network study of the nuclear ground-state spin distribution within a random interaction ensemble

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Nuclear Science and Techniques 2024年第3期35卷 216-227页

作者： Deng Liu Alam Noor A zhen-zhen Qin Yang Lei School of Mathematics and Physics Southwest University of Science and TechnologyMianyang 621010China School of Nuclear Science and Technology Southwest University of Science and TechnologyMianyang 621010China

The distribution of the nuclear ground-state spin in a two-body random ensemble(TBRE)was studied using a general classification neural network(NN)model with two-body interaction matrix elements as input features and the corresponding ground-state spins as labels or output *** quantum many-body system problem exceeds the capability of our optimized NNs in terms of accurately predicting the ground-state spin of each sample within the ***,our NN model effectively captured the statistical properties of the ground-state spin because it learned the empirical regularity of the ground-state spin distribution in TBRE,as discovered by physicists.

关键词： Neural network Two-body random ensemble Spin distribution of nuclear ground state

Design Research of a Novel Aftercool-Humidifier Concept for Humid Air Turbine Cycle

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Journal of Thermal Science 2024年第3期33卷 951-969页

作者： ZHANG Junzheng XU zhen School of Energy and Power Engineering Shandong UniversityJi’nan250061China Shandong Engineering Laboratory for High-efficiency Energy Conservation and Energy Storage Technology&Equipment Shandong UniversityJi’nan250061China

Humid air turbine cycle(HAT)has potential of electrical efficiencies comparable to combined cycle,with lower investment cost and NO_(x) *** typical heat exchanger network of HAT consists of intercooler(if there is),aftercooler,recuperator,economizer and humidifier,which brings higher efficiency but makes the system more *** simplify HAT layout,a novel humidifier concept is proposed by integrating the aftercooler into traditional counter-current *** on this concept,a one-dimensional model including pressure drop and exergy calculation is established to distinguish the thermodynamic and hydrodynamic characteristics,and then the structural parameters,such as the number of rows and columns,tube diameter,pitch and type for a micro HAT are *** results show that the aftercool-humidifier plays the same role as original aftercooler and humidifier,and can match the in-tube air,out-tube air and water stream well with lower *** the case of micro HAT cycle,the volume of heat and mass transfer area can be reduced by 47%compared with traditional *** major thermal resistance occurred in the convection heat transfer process inside the tube;however,using enhanced tube cannot effectively improve the compactness of device.

关键词： humid air turbine cycle humidifier thermodynamic analysis one-dimensional model

Number of Solitons Emerged in the Initial Profile of Shallow Water Using Convolutional Neural Networks

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Journal of Systems Science & Complexity 2024年第2期37卷 463-479页

作者： WANG zhen CUI Shikun School of Mathematical Sciences Dalian University of TechnologyDalian 116024China School of Mathematical Sciences Beihang UniversityBeijing 100191China

The soliton resolution conjecture proposes that the initial value problem can evolve into a dispersion part and a soliton ***,the problem of determining the number of solitons that form in a given initial profile remains unsolved,except for a few specific *** this paper,the authors use the deep learning method to predict the number of solitons in a given initial value of the Korteweg-de Vries(KdV)*** leveraging the analytical relationship between Asech^(2)(x)initial values and the number of solitons,the authors train a Convolutional Neural Network(CNN)that can accurately identify the soliton count from spatio-temporal *** trained neural network is capable of predicting the number of solitons with other given initial values without any additional *** extensive calculations,the authors demonstrate the effectiveness and high performance of the proposed method.

关键词： Convolutional neural network deep learning method KdV equation soliton

NSUN2 mediates distinct pathways to regulate enterovirus 71 replication

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Virologica Sinica 2024年第4期39卷 574-586页

作者： Lishi Liu zhen Chen Kui Zhang Haojie Hao Li Ma Haizhou Liu Baocheng Yu Shuang Ding xueyan Zhang Miao Zhu Xiang Guo Yi Liu Haibin Liu Fang Huang Ke Peng Wuxiang Guan Center for Emerging Infectious Diseases Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhanHubei430071China University of Chinese Academy of Sciences Beijing100049China Hubei Jiangxia Laboratory WuhanHubei430200China

Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various *** the function of m5C deposition is well characterized,other potential roles of NSUN2 in regulating viral replication remain largely *** this study,the m5C modified residues catalyzed by NSUN2 on enterovirus 71(EV71)RNAs were ***2,along with m5C modifications,played multiple roles during the EV71 life *** m5C modified nucleotides increased the translational efficiency and stability of EV71 ***,NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ***,both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were *** together,this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication,and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.

关键词： NSUN2 5-methylcytosine Enterovirus 71 Ubiquitination Pathogenicity

Nuclear charge radius predictions by kernel ridge regression with odd-even effects

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Nuclear Science and Techniques 2024年第2期35卷 94-102页

作者： Lu Tang zhen-Hua Zhang Mathematics and Physics Department North China Electric Power UniversityBeijing 102206China Hebei Key Laboratory of Physics and Energy Technology North China Electric Power UniversityBaoding 071000China

The extended kernel ridge regression(EKRR)method with odd-even effects was adopted to improve the description of the nuclear charge radius using five commonly used nuclear *** are:(i)the isospin-dependent A^(1∕3) formula,(ii)relativistic continuum Hartree-Bogoliubov(RCHB)theory,(iii)Hartree-Fock-Bogoliubov(HFB)model HFB25,(iv)the Weizsacker-Skyrme(WS)model WS*,and(v)HFB25**** the last two models,the charge radii were calculated using a five-parameter formula with the nuclear shell corrections and deformations obtained from the WS and HFB25 models,*** each model,the resultant root-mean-square deviation for the 1014 nuclei with proton number Z≥8 can be significantly reduced to 0.009-0.013 fm after considering the modification with the EKRR *** best among them was the RCHB model,with a root-mean-square deviation of 0.0092 *** extrapolation abilities of the KRR and EKRR methods for the neutron-rich region were examined,and it was found that after considering the odd-even effects,the extrapolation power was improved compared with that of the original KRR *** strong odd-even staggering of nuclear charge radii of Ca and Cu isotopes and the abrupt kinks across the neutron N=126 and 82 shell closures were also calculated and could be reproduced quite well by calculations using the EKRR method.

关键词： Nuclear charge radius Machine learning Kernel ridge regression method