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Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

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Science China(life Sciences) 2024年第4期67卷 698-710页

作者： Runtian Wang Gaigai li Fangyan Gao Feng Xu Xintong li Jian Zhang jinbo li Xiaoxiang Guan Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China State Key Laboratory of Analytical Chemistry for life Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China Department of Medical Oncology Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.

关键词： triple-negative breast cancer c-Myc spherical nucleic acid self-assembly

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A comprehensive study on the heat transfer characteristics of windward bend lattice frame structure

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Propulsion and Power Research 2022年第3期11卷 376-390页

作者： Xiaohui Bai Cunliang liu Changxian Zhang Xianlong Meng jinbo li Xianlong Zhang School of Power and Energy Northwestern Polytechnical UniversityXi’an710072China Shaanxi Key Laboratory of Thermal Sciences in Aero-engine System Xi’an710072China Aero Engine Academy of China Beijing101304China

The windward bend lattice frame structure(WB structure)is characterized by a high heat transfer coefficient and low friction factor.The WB structure can be applied for ther-mal protection system,protecting outer walls of afterburner and nozzles from being damaged by the heating load of hot gas,for air cooling system of the power battery module,dissipating the heat generated during its charging and discharging.In this paper,the heat transfer charac-teristics of the windward bend lattice frame structure have been comprehensively studied.A systematic 3D numerical simulation has been conducted to investigate the effects of the struc-tural parameters of the WB structure,including the pitches in both flow direction and transverse direction,the diameter and the inclination angle of windward bend ligament,on its flow resis-tance and heat transfer enhancement,which has been evaluated by comparing its Nusselt num-ber under an equal pumping power.Furthermore,the contribution of an important parameter,i.e.,the ratio of the interstitial heat transfer rate to the end-wall heat transfer rate(RQ),to the overall heat transfer rate has been fully discussed.As a result,the case of 6 units in the longi-tudinal direction and 2.5 units in the transverse direction,i.e.(nx Z 6,nz Z 2.5)exhibits the best performance in the light of the value of the Nusselt number. Moreover, the structure with aratio of RQ ranges in 4.5e5.0 achieves a better heat transfer performance. Finally, two colorcontour graphs showing an optimal range of Nusselt number coordinated by unit numbers(nx, nz) for pumping powers of 2500 and 3000 have been presented. The graphs correctly reflectthe variation of Nusselt numbers of structures with different nx and nz, and the conclusionsremain consistent with the discussion in sections 4.2 and 4.3, instructing the reasonable selec-tion of structural parameters of a thermal protection system embedded with WB structure.

关键词： Windward bend structure Heat transfer characteristics Flow resistance Thermal protection Nusselt number

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Targeted Degradation of DNA/RNA Binding Proteins via Covalent Hydrophobic Tagging

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CCS Chemistry 2023年第10期5卷 2207-2214页

作者： Yan Wang Jingzi Zhang Jiafang Deng Chengzhi Wang Lei Fang Yan Zhang jinbo li State Key Laboratory of Analytical Chemistry for life Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023 Jiangsu Key Laboratory of Molecular Medicine Chemistry and Biomedicine Innovation Center(ChemBIC)Medical School of Nanjing UniversityNanjing 210093

Targeted protein degradation(TPD)holds great promise for biological inquiry and therapeutic development.However,it still remains elusive to destruct DNA/RNA binding proteins(DBPs/RBPs)previously deemed undruggable.Herein,we report ligandassisted covalent hydrophobic tagging(LACHT)as a modular strategy for TPD of these difficult-totarget proteins.Guided by a noncovalent protein ligand,LACHT leverages a reactive N-acyl-N-alkyl sulfonamide group to covalently label the protein target with a hydrophobic adamantane,which further engages the cellular quality control mechanism to induce proteolytic degradation.Using a smallmolecule ligand,we demonstrated that LACHT allowed TPD of a DBP,bromodomain-containing protein 4,in human leukemia cells with high efficiency.Mechanistic studies revealed that LACHT-mediated TPD dependent on ligand-directed irreversible tagging and the covalently labeled proteins underwent polyubiquitination before removal through both the proteasome and the lysosome.Furthermore,when an RNA ligand was employed,we showed that LACHT also enabled TPD of an RBP,lin28a,leading to upregulation of its downstream let-7 miRNA.This study thus provides a generalizable platform to expand the TPD toolbox for biomedical applications.

关键词： targeted protein degradation covalent labeling hydrophobic tagging DNA/RNA binding proteins miRNA

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Recent advances in cathodes for all-solid-state lithium-sulfur batteries

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Chinese Chemical Letters 2023年第7期34卷 58-69页

作者： Shengbo Yang Bo Wang Qiang Lv Nan Zhang Zekun Zhang Yutong Jing jinbo li Rui Chen Bochen Wu Pengfei Xu Dianlong Wang MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage State Key Laboratory of Urban Water Resource and EnvironmentSchool of Chemistry and Chemical EngineeringHarbin Institute of TechnologyHarbin 150001China

lithium-sulfur(li-S)batteries have been regarded as the candidate for the next-generation energy storage system due to the high theoretical specific capacity(1675 m Ah/g), energy density(2600 Wh/kg)and the abundance of elemental sulfur, but the application of li-S batteries is impeded by a series of problems. Recently, all-solid-state li-S batteries(ASSLSBs) have drawn great attention because many drawbacks such as safety issues caused by metallic lithium anodes and organic liquid electrolytes can be overcome through the use of solid-state electrolytes(SEs). However, not only the problems brought by sulfur cathodes still exist, but more trouble arouses from the interfaces between SEs and cathodes, hampering the practical application of ASSLSBs. Therefore, in order to deal with the problems, enormous endeavors have been done on ASSLSB cathodes during the past few decades, including engineering of cathode active materials, cathode host materials, cathode binder materials and cathode structures. In this review, the electrochemical mechanism and existing problems of ASSLSBs are briefly introduced. Subsequently, the strategies for developing cathode materials and designing cathode structures are presented. Then there follows a brief discussion of SE problems and expectations, and finally, the challenges and perspectives of ASSLSBs are summarized.

关键词： All-solid-state li-S battery Cathode active material Cathode host material Cathode structure Solid-state electrolyte

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Collusion and Economic Growth: A New Perspective on the China Model

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Economic and Political Studies 2013年第2期1卷 18-39页

作者： HUIHUA NIE jinbo li the School of Economics Renmin University of China the Guanghua School of Management Peking University

In this paper,we propose a political-economy model of China that explains both the rapid economic growth and frequent rate of accidents that have occurred in China.The central government delegates authority to the local government to regulate the production activities of the firm.Under information asymmetry,the local government can collude with the firm and choose"bad"technology,the use of which will lead to faster economic growth and more accidents than the use of"good"technology.We characterize optimal equilibrium within collusion contracts,under which the central government will allow collusion when the cost to eliminate collusion is high.We also characterize the optimal collusion-proof contract,under which the payments,reprimands,and taxes that take place between the local government and the firm are endogenously determined.Our predictions on collusion and growth are supported by an empirical study on the coal industry.

关键词： economic growth China model local government collu

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X-ray irradiation selectively kills thymocytes of different stages and impairs the maturation of donor-derived CD4^+CD8^+ thymocytes in recipient thymus

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The Journal of Biomedical Research 2012年第5期26卷 355-364页

作者： jinbo li Hongquan Cai Jianliang Jin Qian Wang Dengshun Miao The Research Center for Bone and Stem Cells Department of Human Anatomy Nanjing Medical University Nanjing Jiangsu 210029 China Department of Preventive Medieine School of Public Health Nanjing Medical University Nanjing Jiangsu 210029 China

The aim of the present study was to determine whether the sensitivity of thymocytes to X-ray radiation depends on their proliferative states and whether radiation impairs the maturation of donor-derived thymocytes in recipient thymus.We assigned 8-week-old C57BL/6J mice into three treatment groups：1） untreated;2） X-ray radiation;3） X-ray radiation plus bone marrow transplantation with donor bone marrow cells from transgenic mice express-ing enhanced green fluorescent protein（GFP） on a universal promoter.After 4 weeks,the size of the thymus,the number and proliferation of thymocytes and ratios of different stage thymocytes were analyzed by immunohisto-chemistry and flow cytometry.The results showed that：1） CD4＋CD8＋ thymocytes were more sensitive to X-ray radiation-induced cell death than other thymocytes;2） the proliferative capacity of CD4＋CD8＋ thymocytes was higher than that of other thymocytes;3） the size of the thymus,the number of thymocytes and ratios of thymo-cytes of different stages in irradiated mice recovered to the normal level of untreated mice by bone marrow trans-plantation;4） the ratio of GFP-positive CD4＋CD8＋ thymocytes increased significantly,whereas the ratio of GFP-positive CD4＋ or CD8＋ thymocytes decreased significantly.These results indicate that the degree of sensitivity of thymocytes to X-ray radiation depends on their proliferative states and radiation impairs the maturation of donor-derived CD4＋CD8＋ thymocytes in recipient thymus.

关键词： thymus radiation CD4^＋CD8^＋ thymocytes sensitivity donor cells

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Photosynthesis, chilling acclimation and the response of antioxidant enzymes to chilling stress in mulberry seedlings

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Journal of Forestry Research 2019年第6期30卷 2021-2029页

作者： Xiaojia liu Nan Xu Yining Wu jinbo li Haixiu Zhong Huihui Zhang College of Horticulture Jilin Agricultural UniversityChangchun 130118People’s Republic of China Natural Resources and Ecology Institute Heilongjiang Academy of SciencesHarbin 150040People’s Republic of China College of Resources and Environment Northeast Agricultural UniversityHarbin 150030Heilongjiang ProvincePeople’s Republic of China

This study investigates the effects of cold-acclimation in conferring chilling tolerance in seedlings of the mulberry(Morus alba) variety ‘Qiuyu’. Changes in photosynthesis and antioxidant enzymes in chilling acclimatized(CA), and non-acclimatized(NA) seedlings were recorded during chilling stress(3 °C) and a recovery period(25 °C) each for 3 days. The results showed that CA plants had higher net photosynthetic rates(P_n), stomatal conductance(G_s), and maximum photochemical efficiency of photosystem Ⅱ(F_v/F_m) in response to chilling stress compared to NA. The seedlings maintained the same trends during the recovery stage. The responses of Q_A reduction degree (1-q_P) and prime electronic transfer rates(F_o) were lower in acclimatized than in non-acclimatized seedlings. Low-temperature acclimation and chilling stress also caused an increase in leaf proline and soluble sugar contents. Leaf malondialdehyde levels were significantly lower while ascorbate peroxidase(APX) activity was significantly higher in acclimatized seedlings, suggesting that elevated osmolytes and APX confer resistance to chilling temperatures. In this study on the response of mulberry seedlings to chilling stress, we also looked at the recovery process. The response to chilling determines whether mulberry leaves can survive under cold temperatures, while the recovery process determines whether photosynthesis can recover as soon as possible to avoid any secondary damage.

关键词： Antioxidant enzyme Chilling acclimation Chilling tolerance Mulberry Photosynthesis

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Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

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Asian Journal of Pharmaceutical Sciences 2021年第6期16卷 784-793页

作者： Yinxian Yang Shiyi Zuo linxiao li Xiao Kuang jinbo li Bingjun Sun Shujun Wang Zhonggui He Jin Sun Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China

Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid peroxidation.However,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis.Herein,a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin(DOX),iron and unsaturated lipid for efficient ferroptosis.By leveraging the coordination effect between DOX and Fe3+,trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method.First,Fe3+could react with the overexpressed GSH in tumor cells,inducing the GSH depletion and Fe2+generation.Second,the cleavage of trisulfide bond could also consume GSH,and the released DOX induces the generation of H2O2,which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis.Third,the formed Fe3+/Fe2+couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis.This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion,ROS generation and lipid peroxidation,providing new sights for efficient cancer therapy.

关键词： Ferroptosis Iron liposome Redox Prodrug

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An improved gravity method to horizontal tectonic stresses and its applications in Tibet

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Geodesy and Geodynamics 2020年第6期11卷 468-473页

作者： Chuang Xu Hangtao Yu Chaolong Yao jinbo li Jianguo Yan Department of Surveying Engineering School of Civil and TransportationGuangdong University of TechnologyGuangzhou 510006China State Key Laboratory of Information Engineering in Surveying Mapping and Remote SensingWuhan UniversityWuhan430079China College of Natural Resources and Environment South China Agricultural UniversityGuangzhou 510642China

It is significant for identifying mass movement patterns to invert horizontal tectonic stresses at different depths underneath Tibet.In recent years,a large number of achievements focusing on two-dimensional tectonic stresses have been obtained from gravity data.However,three-dimensional tectonic stresses in Tibet are still unknown or debatable.Therefore,in the present study an improved method to multilayer horizontal tectonic stresses using gravity observations is developed.The inverted multilayer horizontal tectonic stresses are in agreement with those from previous studies.In addition,rich tectonic structure and development can be revealed from the inverted multilayer horizontal tectonic stresses:(1)the distribution of horizontal tectonic stresses at various depths shows strong correlation with that of the tectonic elements,where major faults and earthquake epicenters are corresponding with stress highs and the stable basins are consistent with stress lows.(2)the mass movement patterns of whole Tibet present clockwise,and the material movement directions in the west and east are approximately southnorth and east-west,respectively.(3)in eastern Tibet,the eastward materials caused by the south-north extrusion between Indian and Eurasian plates are divided into two parts by the stable Sichuan Block,one flowing nearly southeast and the other moving almost northeast.The inverted multilayer horizontal tectonic stresses may provide direct evidences for mass movement patterns in Tibet.

关键词： Gravity Horizontal tectonic stresses Tibet Multilayer

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改良式左炔诺孕酮宫内缓释系统固定治疗子宫腺肌病

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中山大学学报（医学科学版） 2024年第2期45卷 290-296页

作者：李锦波李雪云吴福丽陈淑琴中山大学附属第六医院妇科广东广州510655 广州市黄埔区中六生物医学创新研究院广东广州510655 顺德区第三人民医院妇产科广东顺德528300 中山大学附属第六医院粤西医院//信宜市人民医院妇科广东茂名525300

【目的】介绍改良式左炔诺孕酮宫内缓释系统(LNG-IUS)固定方法,探讨其在治疗既往曾发生LNGIUS脱落的子宫腺肌病患者中的作用。【方法】收集2022年6月至2023年6月因LNG-IUS脱落在3个医疗机构接受改良式LNG-IUS固定的22例子宫腺肌病患者... 详细信息

【目的】介绍改良式左炔诺孕酮宫内缓释系统(LNG-IUS)固定方法,探讨其在治疗既往曾发生LNGIUS脱落的子宫腺肌病患者中的作用。【方法】收集2022年6月至2023年6月因LNG-IUS脱落在3个医疗机构接受改良式LNG-IUS固定的22例子宫腺肌病患者的资料,分析患者的术前病例特征、术中术后并发症及术后LNG-IUS下移或脱落情况,比较术前、术后3月及术后6月患者痛经及月经量的变化。【结果】22例患者平均手术时间(19.51±7.41)min,术中出血(6.71±5.30)mL。13例患者在局部麻醉下进行,9例患者在静脉麻醉下进行。4例患者由住院医生完成,15例患者由主治医师完成,余3例由副主任及以上医师完成。所有患者未发生术中、术后并发症。平均随访时间11.51月,随访期间无患者再次发生LNG-IUS脱落。患者术后1月血红蛋白平均水平显著高于术前(P<0.001)。术后3月及术后6月疼痛评分及月经失血图评分均比术前显著改善(P<0.001)。【结论】改良式LNG-IUS固定是治疗既往发生LNG-IUS脱落的子宫腺肌病患者安全、有效的方法,可有效避免再次发生LNG-IUS脱落。改良式LNG-IUS固定操作简便,可在各级医疗机构中由各级医师施行,具有临床推广价值。

关键词：左炔诺孕酮宫内缓释系统子宫腺肌病改良式固定月经过多痛经

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