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Intelligent nanotherapeutic strategies for the delivery of CRISPR system

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2510-2543页

作者： Chao Chen Wu Zhong Shiyu Du yayao li Yunfei Zeng Kunguo liu Jingjing Yang Xiaoxiang Guan Xin Han Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province School of MedicineHunan Normal UniversityChangsha 410013China Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

关键词： CRISPR system Intelligent delivery Gene editing Endogenous responsive Exogenous control Nanotherapeutic platforms Gene therapy Diseases correction

Subfield Codes of linear Codes from Perfect Nonlinear Functions and Their Duals

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Communications in Mathematical Research 2022年第2期38卷 157-183页

作者： Dabin Zheng Xiaoqiang Wang yayao li Mu Yuan Hubei Key Laboratory of Applied Mathematics and Faculty of Mathematics and StatisticsHubei UniversityWuhan 430062China

Let F_(p)^(m) be a finite field with p^(m) elements,where p is an odd prime and m is a positive ***,[17]and[35]determined the weight distributions of subfield codes with the form C f={((T r(a f(x)+b x)+c)_(x∈F_(p)^(m)),T r(a)):a,b∈F_(p)^(m),c∈F_(p)}for f(x)=x^(2) and f(x)=x p k+1,respectively,where Tr(⋅)is the trace function from F_(p)^(m) to F_(p),and k is a nonnegative *** this paper,we further investigate the subfield code C f for f(x)being a known perfect nonlinear function over F_(p)^(m) and generalize some results in[17,35].The weight distributions of the constructed codes are determined by applying the theory of quadratic forms and the properties of perfect nonlinear functions over finite *** addition,the parameters of the duals of these codes are also *** examples show that some of our codes and their duals have the best known parameters according to the code tables in[16].The duals of some proposed codes are optimal according to the Sphere Packing bound if p≥5.

关键词： Subfield code perfect nonlinear function quadratic form weight distribution Sphere Packing bound

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4224-4234页

作者： Zekun li Yongchun Pan Shiyu Du yayao li Chao Chen Hongxiu Song Yueyao Wu Xiaowei Luan Qin Xu Xiaoxiang Guan Yujun Song Xin Han Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Medicine&Holistic Integrative MedicineJiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative MedicineNanjing University of Chinese MedicineNanjing 210023China College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional MaterialsState Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNajing 210023China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

Near-infrared(NIR)-light-triggered nanomedicine, including photodynamic therapy(PDT)and photothermal therapy(PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania(TiO_(2-x)) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase(HAase) and glutathione(GSH) can readily destroy hyaluronic acid(HA) and disulfide bond and releases the Cas9/sgRNA from TiO_(2-x) to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2(NRF2) and heat shock protein 90a(HSP90a), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_(2-x) demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

关键词： Near infrared phototherapy Gene editing Nuclear factor E2-related factor 2 .Heat shock protein 90c TiO_(2-x) Sensitized phototherapy Nanoprodrug Tumor microenvironment

Author correction to “Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy” [Acta Pharm Sin B (2022) 4224-4234]

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Acta Pharmaceutica Sinica B 2024年第2期14卷 897-899页

作者： Zekun li Yongchun Pan Shiyu Du yayao li Chao Chen Hongxiu Song Yueyao Wu Xiaowei Luan Qin Xu Xiaoxiang Guan Yujun Song Xin Han Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Medicine&Holistic Integrative MedicineJiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative MedicineNanjing University of Chinese MedicineNanjing 210023China College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional MaterialsState Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

The authors regret that there is an error in the article Fig.5E due to the mistake of copying and pasting in the process of assembling figures and negligence in the *** it does not affect the conclusion,it is an obvio... 详细信息

关键词： journal correction conclusion

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光电神经突触器件研究进展

中国科学：信息科学 2020年第6期50卷 892-912页

作者：李雅瑶王越杨德仁皮孝东浙江大学硅材料国家重点实验室和材料科学与工程学院杭州310027

神经形态计算(类脑计算)以其自适应学习、高并行计算和低功耗等优点,被认为是最有希望解决冯·诺依曼(von Neumann)瓶颈的方法之一.实现神经形态计算的重要前提是开发能模拟生物突触行为的神经突触器件.电学神经突触器件是首先发展起来... 详细信息

神经形态计算(类脑计算)以其自适应学习、高并行计算和低功耗等优点,被认为是最有希望解决冯·诺依曼(von Neumann)瓶颈的方法之一.实现神经形态计算的重要前提是开发能模拟生物突触行为的神经突触器件.电学神经突触器件是首先发展起来的神经突触器件,但是它们在统筹考虑带宽、连接、密度等因素下的整体优化面临着很大的挑战.近年来,把光引入神经突触器件,研制光电神经突触器件,为神经突触器件的发展带来了新机遇.对神经突触器件而言,光不仅具备电难以实现的高带宽、低串扰、低功率和无延迟等特性,还可以直接模拟视觉等至关重要的神经行为.光电神经突触器件作为基于光电集成的人工神经网络的基础,有望有力促进高性能和低功耗的神经形态计算的发展.本文主要介绍了光电神经突触器件的基本性能和类别,展示了已经实现的光电神经突触器件的模拟应用,并展望了今后光电神经突触器件的发展.

关键词：光电神经突触器件突触可塑性能耗氧空位离化与去离化载流子俘获与释放

A Value Classification of Electronic Product Reviews Based on Maximum Entropy

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Chinese Journal of Electronics 2016年第6期25卷 1071-1078页

作者： ZUO yayao li Jiejun TANG Yong SHU Zhongmei Faculty of Computer Guangdong University of Technology School of Computer Science South China Normal University School of Education Sun Yat-sen University

Reviews of electronic product are important resources for manufacturers to gather feedbacks from customers. They provide an important reference for customers to make a decision on product purchase. Electronic product reviews with high quality is valuable, and reviews analysis is becoming an open issue. Based on the binary feature function, a maximum entropy classification of electronic product reviews is proposed to identify the valuable reviews. Considering the simpleness of the theme in reviews, a text classifier integrated with the features of descriptive anaphor is provided to enhance the model’s fitting degree. Furthermore, the feature library is constructed by the Term frequency-inverse document frequency(TF-IDF)algorithm to locate the description, and the descriptive anaphors are identified by means of the minimum Inflectional phrase(IP) parsing tree. The experiment shows the proposed classifier has the relatively high stability and precision, which makes the reviews much more usable for manufacturers to make product strategy and for customers to make a decision.

关键词： Maximum entropy Binary feature function Electronic product reviews Review classification Anaphor identification

鲢鱼皮明胶提取方法和谷氨酰胺转氨酶改性对明胶结构和膜性能的影响

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食品科学 2017年第19期38卷 92-99页

作者：郑雅爻马月罗永康李博中国农业大学食品科学与营养工程学院北京100083

研究鲢鱼皮明胶的酶法、酸法、热水法3种常用的工业提取方法对其凝胶强度、黏度以及膜性能指标的影响,在此基础上进一步使用谷氨酰胺转氨酶(transglutaminase,TG)改性以达到改善膜性能的效果。同时以市售猪皮明胶为对照,采用圆二色谱、... 详细信息

研究鲢鱼皮明胶的酶法、酸法、热水法3种常用的工业提取方法对其凝胶强度、黏度以及膜性能指标的影响,在此基础上进一步使用谷氨酰胺转氨酶(transglutaminase,TG)改性以达到改善膜性能的效果。同时以市售猪皮明胶为对照,采用圆二色谱、红外光谱分析3种提取方法对明胶高级结构的影响;通过红外光谱、原子力显微镜分析了鲢鱼皮明胶TG改性前后明胶高级结构和表面结构变化。结果表明,3种提取方法中酶法明胶的比黏度和凝胶强度最大,成膜后的酶法明胶膜抗拉强度最大、断裂延伸率最大、水蒸气透过率最低。继续经过TG改性后,抗拉强度、断裂延伸率指标显著增加(P<0.05),接近猪皮明胶膜,水蒸气透过率进一步降低。圆二色谱及红外光谱结果发现酶法明胶α-螺旋相对含量增加、无规卷曲相对含量减少,并可保留更多的分子内氢键。而TG改性后明胶分子内氨基转变为亚氨基,同时增强了肽链间相互作用。原子力显微镜图像分析结果证明,TG改性的明胶膜具有更为致密均匀的表面结构。明胶膜的机械强度与明胶结构中α-螺旋的含量呈正相关。因此,酶法提取并通过TG改性是一种提高可食性明胶膜性能的有效方法。

关键词：鲢鱼明胶改性膜性能

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融合细粒度实体类型的多特征关系分类算法

计算机工程与应用 2022年第22期58卷 65-71页

作者：左亚尧易彪黎文杰广东工业大学计算机学院广州510006

近年来,基于深度学习的关系分类多集中于注意力机制的改进或语义信息的优化两方面,但此类方法提取的特征往往较为单一,忽略了实体类型对关系分类的影响,且存在语义信息学习不完整等问题。提出一种新的关系分类方法Type-SBNE,针对实体类... 详细信息

近年来,基于深度学习的关系分类多集中于注意力机制的改进或语义信息的优化两方面,但此类方法提取的特征往往较为单一,忽略了实体类型对关系分类的影响,且存在语义信息学习不完整等问题。提出一种新的关系分类方法Type-SBNE,针对实体类型学习任务,引入细粒度的实体类型信息,并通过对每个实体类型中的所有实体向量取平均生成实体类向量,再分别通过实体与句意信息学习获得其对应的特征向量,通过拼接融合得到复合语义特征,最后采用全连接层和Softmax函数来预测实体对之间的关系。Type-SBN基于细粒度的实体类型信息,丰富了实体的特征,有效加强了每个实体在上下文中的表达。实验表明,Type-SBNE模型可更好地完成关系分类任务,效果优于对比方法。

关键词：关系分类 BERT Nyströmformer 细粒度实体类向量

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中文时间关键词识别研究

计算机应用研究 2017年第4期34卷 981-985页

作者：左亚尧龙耀发李杰骏广东工业大学计算机学院广州510006

时态信息广泛应用在自然语言处理、信息检索等领域,而时间关键词识别更是时态信息应用的关键,其直接影响到时态信息的使用。时间信息在文本或句中形式多样性、位置随意性以及边界不确定性等特点成为时间关键词识别任务中的难点。为了解... 详细信息

时态信息广泛应用在自然语言处理、信息检索等领域,而时间关键词识别更是时态信息应用的关键,其直接影响到时态信息的使用。时间信息在文本或句中形式多样性、位置随意性以及边界不确定性等特点成为时间关键词识别任务中的难点。为了解决中文时间关键词的识别问题,通过分析文本语句结构并结合语法结构树提出短语划分方法,将文本转换成短语集从而确定短语边界;在此基础上提出短语向量化表示法,以此构建向量空间;最后,引入谱聚类的聚类思想,将识别问题转换为聚类问题。实验证明,运用该方法进行中文时态关键词识别具有较好的效果。

关键词：时间关键词时间关键词识别谱聚类