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Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

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Acta Pharmaceutica Sinica B 2024年第2期14卷 751-764页

作者： Wen Li jiali Huang Chen shen Weiye Jiang Xi Yang Jingxuan Huang Yueqing Gu Zhiyu Li Yi Ma Jinlei Bian State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of Drug Design and Optimization Department of Medicinal ChemistrySchool of PharmacyChina Pharmaceutical UniversityNanjing 210009China

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs.To address this challenge,we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug,specifically 6-diazo-5-oxo-L-norleucine(DON),using a thioketal linkage(TK).This system enables imaging,chemotherapy,photodynamic therapy,and on-demand drug release upon radiation exposure.The optimized prodrug,DON-TK-BM3,incorporating cyanine dyes as the fluorophore,displayed potent reactive oxygen species release and efficient tumor cell killing.Unlike the parent drug DON,DON-TK-BM3 exhibited no toxicity toward normal cells.Moreover,DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects,including gastrointestinal toxicity,in mice.This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

关键词： Smart prodrug system Glutamineantagonists Immunotherapy Photodynamictherapy Reactive oxygen species Metabolicinhibitor Cyaninedye Non-small-cell lung cancer(NSCLC)

Measurement Uncertainty Analysis of the Rotary-scan Method for the Measurable Dimension of Cylindrical Workpieces

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Instrumentation 2024年第1期11卷 10-17页

作者： jiali Zhao Liang Zhang Dan Wu Bobo shen Qiaolin Li School of Mechanical and Electrical Engineering Lanzhou University of TechnologyLanzhou 730050China shenzhen International Graduate School Tsinghua UniversityShenzhen 518055China

The measurement uncertainty analysis is carried out to investigate the measurable dimensions of cylindrical workpieces by the rotary-scan method in this paper.Due to the difficult alignment of the workpiece with a diameter of less than 3 mm by the rotary scan method,the measurement uncertainty of the cylindrical workpiece with a diameter of 3 mm and length of 50 mm which is measured by a roundness measuring machine,is evaluated according to GUM(Guide to the Expression of Uncertainty in Measurement)as an example.Since the uncertainty caused by the eccentricity of the measured workpiece is different with the dimension changing,the measurement uncertainty of cylindrical workpieces with other dimensions can be evaluated the same as the diameter of 3 mm but with different eccentricity.Measurement uncertainty caused by different eccentricities concerning the dimension of the measured cylindrical workpiece is set to simulate the evaluations.Compared to the target value of the measurement uncertainty of 0.1μm,the measurable dimensions of the cylindrical workpiece can be obtained.Experiments and analysis are presented to quantitatively evaluate the reliability of the rotary-scan method for the roundness measurement of cylindrical workpieces.

关键词： measurement uncertainty rotary-scan cylindrical workpiece various dimensions

Lycorine derivative effectively inhibits the replication of coronaviruses both in vitro and in vivo

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hLife

hLife 2024年第2期2卷 75-87页

作者： Liang shen Jianzhong Zhao Ying Xia Junjie Lu jiali Sun Jian Tang Hui Xing Lijuan Yin Yang Yang Chunhua Wang Department of Clinical Laboratory Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceHubeiChina shenzhen Key Laboratory of Pathogen and Immunity National Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyGuangdongChina Department of Clinical Laboratory Xiangyang No.1 People’s HospitalHubei University of MedicineHubeiChina State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&TechnologyTianjinChina

The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.

关键词： broad-spectrum antiviral drug lycorine derivative Ly-8

OsMLH1 interacts with OsMLH3 to regulate synapsis and interference-sensitive crossover formation during meiosis in rice

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Journal of Genetics and Genomics 2021年第6期48卷 485-496页

作者： Xiaodong Xin Xingwang Li Junkai Zhu Xiaobin Liu Zhenghu Chu jiali shen Changyin Wu National Key Laboratory of Crop Genetic Improvement National Center of Plant Gene Research(Wuhan)Huazhong Agricultural UniversityWuhan 430070China Jiangsu Kingearth Seed Co. Ltd.Yangzhou 225012China

Meiotic recombination is essential for reciprocal exchange of genetic information between homologous chromosomes and their subsequent proper segregation in sexually reproducing organisms. MLH1 and MLH3 belong to meiosis-specific members of the Mut L-homolog family, which are required for normal level of crossovers(COs) in some eukaryotes. However, their functions in plants need to be further elucidated.Here, we report the identification of Os MLH1 and reveal its functions during meiosis in rice. Using CRISPRCas9 approach, two independent mutants, Osmlh1-1 and Osmlh1-2, are generated and exhibited significantly reduced male fertility. In Osmlh1-1, the clearance of PAIR2 is delayed and partial ZEP1 proteins are not loaded into the chromosomes, which might be due to the deficient in resolution of interlocks at late zygotene. Thus, Os MLH1 is required for the assembly of synapsis complex. In Osmlh1-1, CO number is dropped by ~53% and the distribution of residual COs is consistent with predicted Poisson distribution,indicating that Os MLH1 is essential for the formation of interference-sensitive COs(class I COs). Os MLH1 interacts with Os MLH3 through their C-terminal domains. Mutation in Os MLH3 also affects the pollen fertility. Thus, our experiments reveal that the conserved heterodimer Mut Lg(Os MLH1-Os MLH3) is essential for the formation of class I COs in rice.

关键词： Meiosis Crossover OsMLH1 OsMLH3 Rice

慈善捐赠、管理者乐观预期与企业过度投资——基于动态认知偏差视角

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管理工程学报 2024年第2期38卷 77-89页

作者：沈弋吕明晗朱佳立徐光华南京林业大学经济管理学院江苏南京210037 上海国家会计学院上海201702 南京理工大学经济管理学院江苏南京210094

企业慈善捐赠虽然改善了社会整体福利,也能为企业带来多重经济利益,但是其对管理决策所产生的心理效应却常常被忽略。本文采用2009-2019年民营上市公司数据,实证检验了企业慈善捐赠通过扰动管理者心理预期最终影响投资行为的过程。研究... 详细信息

企业慈善捐赠虽然改善了社会整体福利,也能为企业带来多重经济利益,但是其对管理决策所产生的心理效应却常常被忽略。本文采用2009-2019年民营上市公司数据,实证检验了企业慈善捐赠通过扰动管理者心理预期最终影响投资行为的过程。研究发现,慈善捐赠水平较高的企业也更容易过度投资,并且,基于动态认知偏差理论,我们发现管理者过度乐观的认知偏差在慈善捐赠与过度投资之间起到了中介作用,上述关系在经过一系列稳健性检验之后依然成立。在进一步分析中我们发现,上述乐观预期不仅体现在企业投资领域,慈善捐赠较多的公司在研发创新以及市场拓展等方面也更加激进。研究结论拓展了企业慈善捐赠后续效应的相关研究视阈,同时也为企业过度投资的产生机理提供了新的路径解释。

关键词：慈善捐赠认知偏差过度投资乐观预期

TiO2 nanotube arrays decorated with Au and Bi2S3 nanoparticles for efficient Fe3+ ions detection and dye photocatalytic degradation

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材料科学技术：英文版 2020年第4期39卷 28-38页

作者： Jianying Huang jiali shen Shuhui Li Jingsheng Cai Shanchi Wang Yao Lu Jihuan He Claire J.Carmalt Ivan P.Parkin Yuekun Lai College of Chemical Engineering Fuzhou UniversityFuzhou350116China National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow UniversitySuzhou215123China Materials Chemistry Research Centre Department of ChemistryUniversity College LondonLondonUK

Due to increasingly serious environmental problems,many researchers are investigating green cleanenergy to solve the world’s energy supply issues.So the strategy that Au nanoparticles(Au NPs)and bismuth sulfide(Bi2S3)NPs are used to evenly decorate TiO2 nanotube arrays(TiO2 NTAs)was carried out.Composite materials demonstrated enhanced solar light absorption ability and excellent photoelectrochemical performance.This was attributed to the presence of Bi2S3 NPs with a narrow band gap and the decoration with noble metallic Au NPs which resulted in local surface plasmon resonance(LSPR)effects.The Au/Bi2S3@TiO2 NTAs composites exhibit improved photocatalytic activity for the degradation of methylene blue(MB)under irradiation of UV and visible light.Moreover,the Au/Bi2S3@TiO2 NTAs exhibits high fluorescence emission at 822 nm.Due to the better binding affinity between Bi2S3,TiO2 and Fe3+ions,the synthesized nanocomposites exhibit high selectivity to Fe3+ions.The number of binding sites for Au/Bi2S3@TiO2 NTAs was estimated to be 1.41 according to the double logarithmic regression method.The calculated value of"K"was 1862 M-1.Fluorescence emission intensity decreases with increasing concentration(30μM–5000μM).The detection limit of the synthesized sensor is 0.221μM.

关键词： TiO2 nanotube Au Bi2S3 Photocatalysis Fluorescence sensing

High-performance porous carbon foams via catalytic pyrolysis of modified isocyanate-based polyimide foams for electromagnetic shielding

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Nano Research 2022年第8期15卷 6851-6859页

作者： Zhouping Sun Bin shen Yang Li jiali Chen Wenge Zheng Ningbo Key Lab of Polymer Materials Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of Sciences Beijing 100049China College of Chemistry and Pharmaceutical Engineering Huanghuai UniversityZhumadian 463000China

Porous carbon skeletons(PCSs)derived from isocyanate-based aromatic polyimide foams(PIFs)by high-temperature pyrolysis are very promising in the fabrication of high-performance polymer composite foams for electromagnetic interference(EMI)shielding due to their efficient conductive networks and facile preparation process.However,severe volumetric shrinkage and low graphitization degree is not conducive to enhancing the shielding efficiency of the PCSs.Herein,ferric acetylacetonate and carbon-nanotube coating have been introduced in isocyanate-based PIFs to greatly suppress the serious shrinkage during pyrolysis and improve the graphitization degree of the final carbon foams through the Fe-catalytic graphitization process,thereby endowing them with better EMI-shielding performance even at lower pyrolysis temperature compared to the control samples.Moreover,compressible polydimethylsiloxane(PDMS)composite foams with the as-prepared carbon foams as prefabricated PCSs have also been fabricated,which could provide not only stable shielding effectiveness(SE)performance even after a thousand compressions,but also multiple functions of Joule heating,thermal insulation and infrared stealth.This study offers a feasible route to prepare high-performance PCSs in a more energy-efficient manner via PIF pyrolysis,which is very promising in the manufacture of multifunctional conductive polymer composite foams.

关键词： porous carbon skeletons isocyanate-based polyimide foams catalytic graphitization electromagnetic interference shielding multiple functions

Acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation presenting as pericardial effusion

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Blood Science 2023年第4期5卷 274-276页

作者： Yuyan shen jiali Sun Donglin Yang Sizhou Feng State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China

1.INTRODUCTION.Extramedullary leukemic infiltration can occur as a manifestation of relapse.It is,however,rare with fewer than 10 cases of cardiovascular relapse reported in the literature,and it often presents as myeloid sarcoma.1 We report a case of pericardial effusion presenting as an isolated extramedullary relapse(IEMR)of leukemia after allogeneic hematopoietic stem cell transplantation(allo-HSCT).

关键词： relapse hematopoietic myeloid

High-Capacity Transport Associated with Pre- and Post-Haulage in Intermodal Road-Rail Transport

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Journal of Transportation Technologies 2014年第3期4卷 289-301页

作者： Ying Ye jiali shen Rickard Bergqvist Industrial and Financial Management&Logistics Department of Business AdministrationSchool of BusinessEconomics and LawUniversity of GothenburgGoteborgSweden

This paper develops a model for analyzing the potential of longer and heavier vehicles (LHVs) related to pre- and post-haulage in the intermodal rail-road transport chain (IRT). The paper considers the combined economic and emission costs among three different transport networks including intermodal rail-road transport with current Swedish regulatory framework for trucks, intermodal rail-road transport with LHVs, and direct-road transport. The objective is to analyse the potential of high-capacity transport associated with pre- and post-haulage for enhancing the competitiveness of intermodal transport from a full-costs perspective. The model developed is applied to a Swedish context and case study. Research findings reveal that the break-even of the IRT compared to the direct road transport could be significantly lowered, which suggests the LHVs contribute to exploring the market of IRT over smaller flows.

关键词： Intermodal Transport HCT Sustainable Transport Pre-and Post-Haulage Modal Shift