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CRISPR-Cas9 gene editing strengthens cuproptosis/chemodynamic/ferroptosis synergistic cancer therapy

ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 4059-4072页

作者： Wu, Xiaoyu Bai, Zijun Wang, Hui Wang, Hanqing Hou, Dahai Xu, Yunzhu Wo, Guanqun Cheng, Haibo sun, dongdong Tao, Weiwei Nanjing Univ Chinese Med Affiliated Hosp Dept Surg Oncol Nanjing 210029 Peoples R China Nanjing Univ Chinese Med Sch Integrated Med Nanjing 210023 Peoples R China Nanjing Univ Chinese Med Jiangsu Collaborat Innovat Ctr Tradit Chinese Med Nanjing 210023 Peoples R China Nanjing Univ Chinese Med Sch Pharmacol Nanjing 210023 Peoples R China Ningxia Med Univ Sch Pharmacol Yinchuan 750004 Peoples R China

Copper-based nanomaterials demonstrate promising potential in cancer therapy. Cu+ efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione, initiating chemical dynamic therapy (CDT) and ferroptosis. Cuproptosis, a newly identified cell death modality that represents a great prospect in cancer therapy, is activated. However, active homeostatic systems rigorously keep copper levels within cells exceptionally low, which hinders the application of cooper nanomaterials-based therapy. Herein, a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is developed. The Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment, further releasing RNP and Cu+. The liberated Cu+ triggered a Fenton-like reaction for CDT and partially transformed to Cu2+, consuming intracellular GSH and initiating cuproptosis and ferroptosis efficiently. Meanwhile, the release of RNP effectively reduced the expression of copper transporter ATP7A, subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT, cuproptosis, and ferroptosis. Such tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： GSH- and pH-responsive Effective copper delivery CRISPR-Cas9 ATP7A Cuproptosis Chemodynamic Ferroptosis Synergistic therapy FERROPTOSIS COMBINATION

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全国中医药博士生学术论坛入围论文学术热点回顾性分析

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中华中医药杂志 2024年第4期39卷 1914-1918页

作者：张楚楚孙东东李海燕中国中医科学院中医药信息研究所北京100700 南京中医药大学中医学院南京210023

目的:全国中医药博士生学术论坛征文活动(以下简称优博活动)至今已举办14届,是面向广大中医药博士生的征文活动,文章试基于优博入围论文,探析中医药学术热点。方法:采用文献调研法,基于Cite Space分析2018—2023年《中华中医药杂志》优... 详细信息

目的:全国中医药博士生学术论坛征文活动(以下简称优博活动)至今已举办14届,是面向广大中医药博士生的征文活动,文章试基于优博入围论文,探析中医药学术热点。方法:采用文献调研法,基于Cite Space分析2018—2023年《中华中医药杂志》优博活动入围论文研究内容。结果:本研究发现其不仅注重采用先进的科学技术手段对中医药机理进行现代科学阐释,而且也同样重视对临床问题的解决以及中医经典的解读。结论:入围论文在一定程度上代表了中医药前沿的研究水平和创新能力,对入围论文的系统梳理和深入分析,有助于了解中医药行业的研究现状及发展趋势,从而为中医药的进一步发展提供借鉴和方向。

关键词：岐黄杯中医药博士生中医经典机制临床研究

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Biodegradation Kinetics for Pre-treatment of Klebsiella pneumoniae Waste with Autothermal Thermophilic Aerobic Digestion

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Chinese Journal of Chemical Engineering 2010年第6期18卷 905-909页

作者： LIU Jingming sun dongdong LIU Hui NIE Yingbin ZHU Zhirong School of Chemical Engineering Northeast Dianli University Jilin 132012 China Department of Chemistry Tongji University Shanghai 200092 China Department of Chemical Engineering Jilin Vocational College of Industry and Technology Jilin 132013 China

Biodegradation parameters and kinetic characteristics for pre-treating waste strains of Klebsiella pneu-moniae were studied in laboratory scale with an insulated reactor by an innovative technique,autothermal thermo-philic aerobic digestion(ATAD) . Based on an Arrhenius-type equation,an empirical model was developed to corre-late the removal of total suspended solid(TSS) with the initial TSS concentration,influent reaction temperature,aeration rate and stirring rate. The reaction temperatures of the ATAD system could be raised from the ambient temperatures of 25 °C to a maximum temperature of 65 °C. The exponentials for the initial TSS concentration,aeration rate and stirring rate were 1.579,-0.8175 and-0.6549,respectively,and the apparent activation energy was 6.8774 kJ·mol-1. The correlation coefficient for the pre-exponential factor was 0.9223. The TSS removal effi-ciency predicted by the model was validated with an actual test,showing a maximum relative deviation of 10.79%. The new model has a good practicability.

关键词： Klebsiella pneumoniae autothermal thermophilic aerobic digestion biodegradation kinetics empirical model

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吴勉华治疗恶性肿瘤经验

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中华中医药杂志 2024年第4期39卷 1816-1819页

作者：孙东东魏小曼朱玲艳朱叶萍吴勉华(指导) 江苏省中医药防治肿瘤协同创新中心南京210023 南京中医药大学中医学院南京210023 南京中医药大学第一临床医学院南京210023

总结吴勉华教授治疗恶性肿瘤的临床经验。“正气不足,邪毒内蕴”是恶性肿瘤发生发展的核心病机,正虚以气阴两虚、脾胃虚弱为主;邪毒有郁、热、痰、湿、瘀、毒之不同。提出以扶正固本、祛邪解毒为治疗原则,以益气养阴为治疗根本,抗癌解... 详细信息

总结吴勉华教授治疗恶性肿瘤的临床经验。“正气不足,邪毒内蕴”是恶性肿瘤发生发展的核心病机,正虚以气阴两虚、脾胃虚弱为主;邪毒有郁、热、痰、湿、瘀、毒之不同。提出以扶正固本、祛邪解毒为治疗原则,以益气养阴为治疗根本,抗癌解毒为治疗核心,理气解郁贯穿全程,并灵活运用活血祛瘀法、化湿泄浊法、化痰散结法、健脾和胃法等,辨病与辨证、整体与局部相结合,以减轻患者症状、延长患者生存期、改善患者生活质量等。

关键词：恶性肿瘤治法要点名医经验抗癌解毒吴勉华

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Isolation,structural determination and cytotoxic activity of two new ceramides from the root of Isatis indigotica

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Science China Chemistry 2009年第5期52卷 621-625页

作者： sun dongdong DONG WeiWei LI Xiang ZHANG HanQing Pharmaceutical College Nanjing University of Chinese MedicineNanjing 210046China College of Chemistry and Chemical Engineering Nanjing University of TechnologyNanjing 210009China Institute of Botany Jiangsu Province and Chinese Academy of SciencesNanjing 210014China

Two new ceramides were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as 1-O-β-D-glucopyranosyl-(2S, 3R)-N-(2'-hydroxypentacosanoyl)-octadeca-11E-sphingenine (1) and 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhe xacosanoyl)-octadeca-11E-sphingenine (2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.

关键词： Isatis indigotica ceramides cytotoxic activity

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Photodimerization of azaanthracene derivatives mediated by cucurbit[10]uril

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Chinese Chemical Letters 2022年第12期33卷 5124-5127页

作者： Huaxing Li Xianchen Hu Fengbo Liu dongdong sun Yong Wu Simin Liu School of Chemistry and Chemical Engineering Wuhan University of Science and TechnologyWuhan 430081China The State Key Laboratory of Refractories and Metallurgy Institute of Advanced Materials and NanotechnologyWuhan University of Science and TechnologyWuhan 430081China

Challenges of achieving efficient photodimerization of azaanthracene derivatives remain due to the low selectivity and slow reaction *** this paper,cucurbit[10]uril(CB[10]),with the largest rigid and hydrophobic cavity among CB[n]s,was used to affect the photodimerization reaction of four water-soluble 1-(2-)substituted azaanthracene derivatives(1-4).It revealed that 1-4 could form 1:2 host-guest complexes with CB[10]in aqueous *** of 1 in the presence of 0.5 *** CB[10]selectively produced a head-to-tail(anti-HT)photodimer *** for 2-4,CB[10]acted as a nanoreactor accelerating their photodimerization reaction in *** results suggest that photodimerization of azaanthracene derivatives could be promoted by the CB[10]-based host-guest strategy with high efficiency and selectivity.

关键词： Supramolecular nanoreactor Cucurbituril Azaanthracene Photodimerization Host-guest interaction

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Numerical study on the cavity dynamics for vertical water entries of twin spheres

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Defence Technology（防务技术） 2024年第2期32卷 459-472页

作者： Xu Wang Xujian Lyu Ruisheng sun dongdong Tang School of Energy and Power Engineering Nanjing University of Science and TechnologyNanjing210094China Shanghai Institute of Spacecraft Equipment Shanghai200240China

In this study, a three dimensional(3D) numerical model of six-degrees-of-freedom(6DOF) is applied to simulate the water entries of twin spheres side-by-side at different lateral distances and time *** turbulence structure is described using the shear-stress transport k-ω(SST k-ω) model, and the volume of fluid(VOF) method is used to track the complex air-liquid interface. The motion of spheres during water entry is simulated using an independent overset grid. The numerical model is verified by comparing the cavity evolution results from simulations and experiments. Numerical results reveal that the time interval between the twin water entries evidently affects cavity expansion and contraction behaviors in the radial direction. However, this influence is significantly weakened by increasing the lateral distance between the two spheres. In synchronous water entries, pressure is reduced on the midline of two cavities during surface closure, which is directly related to the cavity volume. The evolution of vortexes inside the two cavities is analyzed using a velocity vector field, which is affected by the lateral distance and time interval of water entries.

关键词： Twin water entries Side-by-side Cavity Numerical simulation

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基于学科特点探讨方剂学研究的若干问题

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中华中医药杂志 2024年第2期39卷 609-612页

作者：安黎谭峰李梦雯闫秋莹黄仕文程海波樊巧玲孙东东南京中医药大学中医学院南京210023 国家中医药管理局名医验方评价与转化重点研究室南京210023

方剂学是关于中医遣药制方理论及其临床应用知识的学科,是中医学理、法、方、药体系的重要组成部分。文章基于方剂学科特点,从发展中医学理论知识体系,提升中医临床诊疗效能,助力中医药成果转化3个方面阐述了方剂学研究的主要目标与任务... 详细信息

方剂学是关于中医遣药制方理论及其临床应用知识的学科,是中医学理、法、方、药体系的重要组成部分。文章基于方剂学科特点,从发展中医学理论知识体系,提升中医临床诊疗效能,助力中医药成果转化3个方面阐述了方剂学研究的主要目标与任务,进而分析当前方剂学科在理论、临床及基础研究方面存在的不足之处,最后尝试提出相应解决办法和发展方向,以期为方剂学学科建设及相关研究提供参考或借鉴。

关键词：方剂学学科科学研究问题建议

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仔猪腹泻的病因及防治措施

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天津农林科技 2024年第4期 29-32页

作者：孙冬冬叶桂煊张双喜孙涛哈子明天津市动物疫病预防控制中心天津300402

仔猪腹泻可导致仔猪生长速度降低甚至造成高病死率,为科学防治仔猪腹泻,文章针对仔猪发生腹泻的病因进行了分析,发现导致仔猪腹泻的传染性病因包括病毒性病因、细菌性病因、霉菌及其毒素性病因、寄生虫性病因;导致仔猪腹泻的非传染性病... 详细信息

仔猪腹泻可导致仔猪生长速度降低甚至造成高病死率,为科学防治仔猪腹泻,文章针对仔猪发生腹泻的病因进行了分析,发现导致仔猪腹泻的传染性病因包括病毒性病因、细菌性病因、霉菌及其毒素性病因、寄生虫性病因;导致仔猪腹泻的非传染性病因包括中毒、过食、气候、饲养管理、兽医卫生操作等。根据仔猪腹泻的发生原因,提出了加强引入仔猪群的检验检疫与本土驯化、强化猪场的生物安全措施、定期对相关疫病进行免疫与监测、合理使用抗菌药和抗寄生虫药、保障猪群饮(食)质量、选择品质合格的添加剂、科学合理使用兽药等措施。

关键词：仔猪腹泻病因防治

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The enhanced permeability and retention effect based nanomedicine at the site of injury

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Nano Research 2020年第2期13卷 564-569页

作者： Yingjun Liu dongdong sun Qin Fan Qingle Ma Ziliang Dong Weiwei Tao Huiquan Tao Zhuang Liu Chao Wang Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-based Functional Materials and DevicesSoochow UniversitySuzhou 215123China Collaborative Innovation Center of Jiangsu Province of Cancer Prevention and Treatment of Chinese Medicine School of Integrated Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210023China

The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past *** we unexpectedly observed the similar"EPR effect"at the site of *** found that the temporary dilated and leaky blood vessels caused by the potent vasodilator histamine in response to injury allowed the injected nanoparticles to pass through the vasculature and reached the injured *** finding shows the potential underline mechanism of"EPR effect"at the injured *** loading with antibiotics,we further demonstrated a new strategy for prevention of infection at the site of injury.

关键词： enhanced permeability retention(EPR)effect injured tissue polymeric nanoparticles histamine immune response

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