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Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms

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Asian Journal of pharmaceutical Sciences 2024年第3期19卷 164-180页

作者： Xilong Cui Fanhui Liu Shuang Cai Tingting Wang Sidi Zheng Xinshu Zou Linlin Wang Siqi He Yanhua Li Zhiyun Zhang College of veterinary Medicine Northeast Agricultural University Heilongjiang key laboratory for Animal Disease Control and pharmaceutical development

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm ***-based nanoplatform is a promising emerging approach for treatment of biofilm ***,their therapeutic efficacy was restricted by the low drug loading capacity and lack of ***,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized *** obtained ISL-G2loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr *** NPs maintained their negatively charged surface,thus prolonging the blood circulation *** response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the ***,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm *** in vivo study was performed on a MRSA biofilm infected wound *** phytochemical-based system led to～2log CFU (>99%) reduction of biofilm MRSA as compared to untreated wound (P<0.001)with negligible biotoxicity in *** phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

关键词： MRSA biofilm Isoliquiritigenin Dimer prodrug Charge adaptive Responsive nanoparticles

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Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H:quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase

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Chinese Journal of Natural Medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia SUN Huiyong HAO Haiping ZHANG Bo XU Xiaowei State key laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

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Evolutionary dynamics and comparative pathogenicity of clade 2.3.4.4b H5 subtype avian influenza viruses,China,2021–2022

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Virologica Sinica 2024年第3期39卷 358-368页

作者： Siru Lin Junhong Chen Ke Li Yang Liu Siyuan Fu Shumin Xie Aimin Zha Aiguo Xin Xinyu Han Yuting Shi Lingyu Xu Ming Liao Weixin Jia National Avian Influenza Para-Reference laboratory Guangdong Engineering Laboratory for Medicament of Zoonosis Prevention and ControlKey Laboratory of Zoonoses Prevention and Control of Guangdong ProvinceLaboratory for Lingnan Modern AgricultureCollege of Veterinary MedicineSouth China Agricultural UniversityGuangzhou510642China key laboratory of Zoonoses Key Laboratory of Animal Vaccine DevelopmentMinistry of AgricultureGuangzhou510642China Institute of Poultry Management and Diseases Yunnan Animal Science and Veterinary InstituteKunming650000China

The recent concurrent emergence of H5N1,H5N6,and H5N8 avian influenza viruses(AIVs)has led to significant avian mortality *** 2020,frequent human-animal interactions have been *** gain insight into the novel H5 subtype AIVs(i.e.,H5N1,H5N6 and H5N8),we collected 6102 samples from various regions of China between January 2021 and September 2022,and identified 41 H5Nx *** analyses on the evolution and biological properties of these isolates were *** analysis revealed that the 41 H5Nx strains belonged to clade 2.***.4.4b,with 13 related to H5N1,19 to H5N6,and 9 to *** based on global 2.***.4.4b viruses showed that all the viruses described in this study were likely originated from H5N8,exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015–2022 worldwide.H5N1 showed a higher rate of evolution in 2021–2022 and more sites under positive selection pressure in 2015–*** antigenic profiles of the novel H5N1 and H5N6 exhibited notable *** hemagglutination inhibition assay suggested that some A(H5N1)viruses may be antigenically distinct from the circulating H5N6 and H5N8 *** challenge assays demonstrated that the H5N8 virus(21GD001_H5N8)displayed the highest pathogenicity in mice,followed by the H5N1 virus(B1557_H5N1)and then the H5N6 virus(220086_H5N6),suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian *** on the above results,we speculate that A(H5N1)viruses have a higher risk of emergence in the ***,these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.***.4.4b,contributing to a better understanding of designing more effective strategies for the prevention and control of novel H5 AIVs.

关键词： Avian influenza virus(AIV) H5 subtypes AIVs Evolutionary Pathogenicity

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Analysis method and experimental study of ice accumulation detection signal based on Lamb waves

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Chinese Journal of Aeronautics 2024年第8期37卷 388-403页

作者： Yanxin ZHANG Hongjian ZHANG Xian YI Binrui WU Xianlei GUAN Jianjun XIONG key laboratory of Icing and Anti/De-icing China Aerodynamics Research and Development CenterMianyang 621000China State key laboratory of Aerodynamics China Aerodynamics Research and Development CenterMianyang 621000China

A quantitative identification method for in-flight icing has the capability to significantly enhance the safety of aircraft *** guided waves have the unique advantage of detecting icing in a relatively large area,but quantitative identification of ice layers is a *** this paper,a quantitative identification method of ice accumulation based on ultrasonic guided waves is ***,a simulation model for the wave dynamics of piezoelectric coupling in three dimensions is established to analyze the propagation characteristics of Lamb waves in a structure consisting of an aluminum plate and an ice *** wavelet transform method is utilized to extract the Time of Flight(ToF)or Time of Delay(ToD)of S_(0)/B_(1) mode waves,which serves as a characteristic parameter to precisely determine and assess the level of ice ***,an experimental system is developed to evaluate the feasibility of Lamb waves-based icing real-time detection in the presence of spray ***,a combination of the Hampel median filter and the moving average filter is developed to analyze ToF/ToD *** simulation results reveal a positive correlation between geometric dimensions(length,width,thickness)of the ice layer and ToF/ToD of B1 mode waves,indicating their potential as indicators for quantifying ice *** results of real-time icing detection indicate that ToF/ToD will reach greater peak values with the growth of the arbitrary-shaped ice layer until saturation to effectively predict the simulation *** study lays a foundation for the practical application of quantitative icing detection via ultrasonic guided waves.

关键词： Ice Ice accumulation Ultrasonic sensor Ultrasonic guided wave Lamb wave Wavelet transform

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Building a domain-specific compiler for emerging processors with a reusable approach

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Science China(Information Sciences) 2024年第1期67卷 20-38页

作者： Mingzhen LI Yi LIU Bangduo CHEN Hailong YANG Zhongzhi LUAN Depei QIAN State key laboratory of Software development Environment School of Computer Science and Engineering Beihang University

High-performance computing and deep learning domains have been motivating the design of domain-specific *** these processors can provide promising computation capability,they are notorious for exotic programming *** improve programming productivity and fully exploit the performance potential of these processors,domain-specific compilers(DSCs) have been ***,building DSCs for emerging processors requires tremendous engineering efforts because the commonly used compilation stack is difficult to be *** to the advent of multilevel intermediate representation(MLIR),DSC developers can leverage reusable infrastructure to extend their customized functionalities without rebuilding the entire compilation *** this paper,we further demonstrate the effectiveness of MLIR by extending its reusable infrastructure to embrace a heterogeneous many-core processor(Sunway processor).In particular,we design a new Sunway dialect and corresponding backend for the Sunway processor,fully exploiting its architectural advantage and hiding its programming *** show the ease of building a DSC,we leverage the Sunway dialect and existing MLIR dialects to build a stencil compiler for the Sunway *** experimental results show that our stencil compiler,built with a reusable approach,can even perform better than state-of-the-art stencil compilers.

关键词： domain-specific compiler emerging processor reusable dialect performance optimization MLIR

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An anti-icing scaling method for wind tunnel tests of aircraft thermal ice protection system

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Chinese Journal of Aeronautics 2024年第6期37卷 1-6页

作者： Yu LIU Qiang WANG Xian YI Ningli CHEN Jinghao REN Weihao LI key laboratory of Icing and Anti/de-icing China Aerodynamics Research and Development CenterMianyang 621000China State key laboratory of Aerodynamics Mianyang 621000China

The efficiency of the aircraft Ice Protection Systems(IPSs)needs to be verified through icing wind tunnel ***,the scaling method for testing the IPSs has not been systematically established yet,and further research is *** the present study,a scaling method specifically designed for thermal IPSs was derived from the governing equation of thin water *** scaling parameters were adopted to address the heat and mass transfer involved in the thermal anti-icing *** method validation,icing wind tunnel tests were conducted using a jet engine nacelle model equipped with a bleed air *** non-dimensional surface temperature and runback ice closely matched for both the reference and scaled *** validation confirms that the scaling method is capable of achieving the similarity of surface temperature and the runback ice *** anti-icing scaling method can serve as an important supplement to the existing icing similarity theory.

关键词： Scaling method Ice protection system Water film Anti-icing test Icing wind tunnel

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Structure-guided isolation of anti-neuroinflammatory sesquiterpene coumarins from Ferula sinkiangensis

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Chinese Journal of Natural Medicines 2024年第7期22卷 643-653页

作者： DANG Wen GUO Tingting ZHOU Di MENG Qingqi FANG Mingxia CHEN Gang LIN Bin HOU Yue LI Ning School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning ProvinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110016China College of Life and Health Sciences Northeastern UniversityShenyang 110004China School of pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders,inflammation,tumors,various cancers,and alopecia *** primary bioactive constituents,sesquiterpene coumarins,have demonstrated notable therapeutic potential against *** this study,a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of *** compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques,including calculated electronic circular dichroism(ECD).Anti-neuroinflammatory assays revealed that compounds 2,3,and 6 significantly inhibited nitric oxide(NO)production in lipopolysaccharide(LPS)-stimulated BV2 microglial cells,with IC_(50)values ranging from 1.63 to 12.25μmol·L^(−1).

关键词： Ferula sinkiangensis Sesquiterpene coumarins Structure elucidation Anti-neuroinflammatory activity

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Rapid discovery of two unprecedented meroterpenoids from Daphne altaica *** molecular networking integrated with MolNetEnhancer and Network Annotation Propagation

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Chinese Chemical Letters 2024年第8期35卷 294-298页

作者： Wei-Yu Zhou Zi-Han Xi Ning-Ning Du Li Ye Ming-Hao Jiang Jin-Le Hao Bin Lin Guo-Dong Yao Xiao-Xiao Huang Shao-Jiang Song key laboratory of Computational Chemistry-Based Natural Antitumor Drug Research&development Liaoning ProvinceEngineering Research Center of Natural Medicine Active Molecule Research&DevelopmentLiaoning ProvinceKey Laboratory of Natural Bioactive Compounds Discovery&ModificationShenyangSchool of Traditional Chinese Materia Medic1Shenyang Pharmaceutical UniversityShenyang 110016China key laboratory of Structure-Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China

Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.***.1.0^(2,6).0^(8,13)]pentadecane and tetracyclo[5.***.0.1^(2,5).2^(4,11)]tridecane central frameworks were iso-lated from Daphne altaica Pall.,representing two types of unparalleled meroterpenoid *** struc-tures were elucidated by extensive spectroscopic analysis,nuclear magnetic resonance(NMR)calcula-tions,DP4+analysis and electronic circular dichroism(ECD)*** plausible biosynthetic path-ways for 1 and 2 were ***,2 exerted potent neuroprotective activities which were su-perior to trolox at 12.5 and 25μmol/***,1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than *** docking simulations were performed to explore the inter-molecular interaction of compounds 1 and 2 with *** bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.

关键词： Daphne altaica Pall. Molecular networking MolNetEnhancer NAP Unprecedented meroterpenoid frameworks Neuroprotective activities Acetylcholinesterase inhibitors

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The age of vanadium-based nanozymes: Synthesis, catalytic mechanisms, regulation and biomedical applications

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Chinese Chemical Letters 2024年第4期35卷 52-60页

作者： Shuaiwen Li Zihui Chen Feng Yang Wanqing Yue Department of Chemistry Key Laboratory of Biomedical Functional MaterialsSchool of ScienceChina Pharmaceutical UniversityNanjing 211198China key laboratory of Drug Quality Control and Pharmacovigilance(China pharmaceutical University) Ministry of EducationNanjing 211198China

Nanomaterials with enzyme-mimic(nanozyme) activity have garnered considerable attention as a potential alternative to natural enzymes, thanks to their low preparation cost, high activity, ease of preservation, and unique physicochemical properties. Vanadium(V) is a transition metal that integrates the benefits of valence-richness, low cost, and non-toxicity, making it a desirable candidate for developing a range of emerging nanozymes. In this review, we provide the first systematic summary of recent research progress on V-based nanozymes. First, we summarize the preparation of V-based nanozymes using both top-down and bottom-up synthesis methods. Next, we review the mechanism of V-based nanozymes that mimic the activity of various enzymes. We then discuss methods for regulating V-based nanozyme activity, including morphology, size, valence engineering, defect engineering, external triggering, and surface engineering. Afterward, we outline various biomedical applications, including therapeutic, anti-inflammatory, antibacterial, and biosensing. Finally, we prospect the challenges and countermeasures for V-based nanozymes based on their development. By summarizing recent research progress on V-based nanozymes, we hope to provide useful insights for researchers to further explore their potential applications and overcome their existing challenges.

关键词： Vanadium Nanozymes Catalytic mechanisms Biomedical applications Regulation

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Emerging tropane alkaloids:Global development and potential health threats

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Food Quality and Safety 2024年第1期8卷 12-26页

作者： Zile Wang Shiqi Chen Pimiao Zheng Zhenhui Ren Huixia Zhang Jing Zhang Bing Shao Congming Wu Haiyang Jiang Department of veterinary Pharmacology and Toxicology Beijing Key Laboratory of Detection Technology for Animal-Derived Food SafetyBeijing Laboratory for Food Quality and SafetyNational Key Laboratory of Veterinary Public Health and SafetyCollege of Veterinary MedicineChina Agricultural UniversityBeijingChina. College of veterinary Medicine Shandong Agricultural UniversityTaianChina. Tianjin key laboratory of Agricultural Animal Breeding and Healthy Husbandry College of Animal Science and Veterinary MedicineTianjin Agricultural UniversityTianjinChina Beijing key laboratory of Diagnostic and Traceability Technologies for Food Poisoning Beijing Center for Disease Prevention and ControlBeijingChina.

Tropane alkaloids(TAs)are a kind of plant secondary metabolite that mainly originate from *** have potent anticholinergic activity,and are well-known anticholinergic drugs,but have also been reported as plant *** studies have been conducted on TAs,but no scientometric research has been *** study aimed to expound the knowledge network and development of the feld of TAs and predict the emerging development topics based on *** particular,this research combined VOSviewer and CiteSpace for visualization and covered 1,298 related scientifc publications(1953–2022).The research on TAs is rapidly developing,with the participation of 86 countries,1,129 research institutions,and 4,087 ***,the University of Geneva,and *** are the most productive country,institution,and researcher,***,the main research topics on TAs include biosynthesis,in vitro synthesis,chemical synthesis,and determination *** 2018,the monitoring of TAs in food related to human health has shown citation burst characteristics,which is considered an emerging development trend in the *** fndings of this study will enable researchers to quickly tap into the knowledge background/structure of TAs from massive data to provide a reference for further research.

关键词： Tropane alkaloids bibliometrics biosynthesis in vitro synthesis chemical synthesis determination contamination food safety

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