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CRISPR/Cas9 therapeutics:progress and prospects

Signal Transduction and Targeted Therapy 2023年第2期8卷 558-580页

作者： Tianxiang li Yanyan Yang Hongzhao Qi Weigang Cui lin Zhang Xiuxiu Fu Xiangqin He Meixin liu pei-feng li Tao Yu Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityNo.38 Dengzhou Road266021QingdaoPeople’s Republic of China Department of Immunology School of Basic MedicineQingdao University266021QingdaoPeople’s Republic of China Department of Cardiology People’s Hospital of RizhaoNo.126 Taian Road276827RizhaoPeople’s Republic of China Department of Microbiology Linyi Center for Disease Control and Prevention276000LinyiPeople’s Republic of China Department of Cardiac Ultrasound The Affiliated Hospital of Qingdao University266000QingdaoPeople’s Republic of China

Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency.A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during ***,strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking,and nonviral vectors with target recognition functions may be the focus of future *** and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene *** are both varied and complex,and the choice of appropriate gene-editing methods and delivery vectors for different diseases is ***,there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease *** paper reviews the current developments in three aspects,namely,gene-editing type,delivery vector,and disease ***,this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.

关键词： CRISPR/Cas9 editing delivery

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Small-molecule 7,8-dihydroxyflavone counteracts compensated and decompensated cardiac hypertrophy via AMPK activation

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Journal of Geriatric Cardiology 2022年第11期19卷 853-866页

作者： Peng-Zhou HANG pei-feng li Jie liU feng-feng li Ting-Ting CHEN Yang PAN Man-Ru ZHANG Hua-Qing YU Hong-Yu JI Zhi-Min DU Jing ZHAO Institute of Clinical Pharmacology the Second Affiliated Hospital of Harbin Medical University(University Key Laboratory of Drug ResearchHeilongjiang Province)HarbinChina Department of Pharmacy Clinical Medical CollegeYangzhou UniversityNorthern Jiangsu People's HospitalYangzhouChina Department of Pharmacology Harbin Medical UniversityHarbinChina State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Department of Cardiology the First Affiliated Hospital of Harbin Medical UniversityHarbinChina

BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure.7,8-Dihydroxyflavone(7,8-DHF)is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor *** present study aimed to explore the potential role of 7,8-DHF in cardiac *** Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol(ISO)with or without 7,8-DHF,respectively.F-actin staining was performed to calculate the cell *** levels of hypertrophic markers,including ANP,BNP,andβ-MHC,were ***,hematoxylin-eosin staining,and transmission electron microscopy were used to examine the cardiac function,histology,and ultrastructure of *** levels of mitochondria-related factors,such as adenosine monophosphate-activated protein kinase(AMPK),and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),were *** 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy,diminished the cross-sectional area,and alleviated the mitochondrial disorders of ***,7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated *** addition,7,8-DHF activated AMPK and PGC-1αsignals without affecting the protein levels of mitochondrial dynamics-related *** effects of 7,8-DHF were eliminanted by Compound C,an AMPK *** These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling,providing a potential agent for the treatment of pathological cardiac hypertrophy.

关键词： cardiac hypertrophy inhibited

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Decohesion of graphene from a uniaxially-stretched substrate:Failure analysis of a frictional adhesive interface

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Friction 2024年第3期12卷 510-521页

作者： Bo PENG Chaochen XU Qingao WANG pei ZHAO Xiqiao feng Qunyang li AML Department of Engineering MechanicsTsinghua UniversityBeijing 100084China State Key Laboratory of Tribology in Advanced Equipment Tsinghua UniversityBeijing 100084China Center for X-Mechanics and Institute of Applied Mechanics Zhejiang UniversityHangzhou 310027China State Key Laboratory of Fluid Power and M

Composite structures consisting of two-dimensional(2D)materials deposited on elastic substrates have a wide range of potential applications in flexible *** such devices,robust 2D film/substrate interfacial adhesion is essential for their reliable performance when subjected to external thermal and mechanical *** better understand the strength and failure behavior of the 2D film/substrate interfaces,two types of graphene/polymer samples with distinct interfacial adhesion properties are fabricated and tested by uniaxially stretching the *** on the interfacial adhesion,two drastically different debonding rates are observed,i.e.,rapid snap-through debonding and more progressive crack *** by the experimental observation,we propose an improved shear-lag model with a trapezoidal-shaped cohesive zone to derive an analytical solution for the decohesion *** theoretical model reveals that the decohesion behavior of the frictional adhesive interface is governed by three dimensionless ***,the dimensionless length of the film essentially determines the decohesion rate;while the other two parameters affect the critical substrate strain to initiate *** fitting the experimental data with the theoretical model,the intrinsic adhesion properties of the two samples are obtained with physically meaningful *** work offers an analytical solution to describing the decohesion behavior of general thin film/substrate systems with a frictional adhesive interface,which is beneficial for characterizing and optimizing the mechanical properties of various thin film/polymer devices.

关键词： film/substrate systems adhesion frictional sliding interface decohesion cohesive-zone model

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Augmenting Trigger Semantics to Improve Event Coreference Resolution

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Journal of Computer Science & Technology 2023年第3期38卷 600-611页

作者：宦敏徐昇李培峰 School of Computer Science and Technology Soochow UniversitySuzhou 215000China

Due to the small size of the annotated corpora and the sparsity of the event trigger words, the event coreference resolver cannot capture enough event semantics, especially the trigger semantics, to identify coreferential event mentions. To address the above issues, this paper proposes a trigger semantics augmentation mechanism to boost event coreference resolution. First, this mechanism performs a trigger-oriented masking strategy to pre-train a BERT (Bidirectional Encoder Representations from Transformers)-based encoder (Trigger-BERT), which is fine-tuned on a large-scale unlabeled dataset Gigaword. Second, it combines the event semantic relations from the Trigger-BERT encoder with the event interactions from the soft-attention mechanism to resolve event coreference. Experimental results on both the KBP2016 and KBP2017 datasets show that our proposed model outperforms several state-of-the-art baselines.

关键词： event coreference resolution trigger semantics augmentation information interaction

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Three-Layer Joint Modeling of Chinese Trigger Extraction withConstraints on Trigger and Argument Semantics

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Journal of Computer Science & Technology 2017年第5期32卷 1044-1056页

作者： pei-feng li Guo-Dong Zhou School of Computer Science and Technology Soochow University Suzhou 215006 China

As a subtask of information extraction (IE), which aims to extract structured information from texts, event extraction is to recognize event trigger mentions of a predefined event type and their arguments. In general, event extraction can be divided into two subtasks: trigger extraction and argument extraction. Currently, the frequent existences of unannotated trigger mentions and poor-context trigger mentions impose critical challenges in Chinese trigger extraction. This paper proposes a novel three-layer joint model to integrate three components in trigger extraction, i.e., trigger identification, event type determination, and event subtype determination. In this way, different kinds of evidence on distinct pseudo samples can be well captured to eliminate the harmful effects of those un-annotated trigger mentions. In addition, this paper introduces various types of linguistically driven constraints on the trigger and argument semantics into the joint model to recover those poor-context trigger mentions. The experimental results show that our joint model significantly outperforms the state-of-the-art Chinese trigger extraction and Chinese event extraction as a whole.

关键词： information extraction trigger extraction joint modeling trigger semantics argument semantics

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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： li-hua Zhu Yu-pei liang lian Yang feng Zhu li-jun Jia He-gen li Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Cancer Institute of Traditional Chinese Medicine Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Laboratory Medicine Huadong HospitalFudan UniversityShanghai 200237China

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate,colorectal and gastric cancers;however,its efficacy for inhibiting the proliferation of lung cancer cells is largely *** study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC)and elucidates the underlying molecular ***:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation ***-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide *** elucidate the role of cycloastragenol in the induction of apoptosis,apoptosis-related proteins were examined using Western *** and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer *** techniques,including small interfering RNA technology,were used to investigate the underlying *** effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor ***:Cycloastragenol triggered both autophagy and ***,cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA),a critical apoptosis-related ***,cycloastragenol induced a protective autophagy response through modulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/unc-51-like autophagy-activating kinase(ULK1)/mammalian target of rapamycin(mTOR)***:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in *** insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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Efficient and stable PtFe alloy catalyst for electrocatalytic methanol oxidation with high resistance to CO

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Journal of Energy Chemistry 2024年第3期90卷 327-336,I0008页

作者： Qian Yang Sifan Zhang fengshun Wu lihua Zhu Guang li Mingzhi Chen An pei Yingliang feng Jiangxi Provincial Key Laboratory of Functional Molecular Materials Chemistry College of Chemistry and Chemical EngineeringFaculty of Materials Metallurgy and ChemistryJiangxi University of Science and TechnologyGanzhou 341000JiangxiChina College of Chemistry and Chemical Engineering Xiamen UniversityXiamen 361005FujianChina

Direct methanol fuel cells(DMFC) are widely considered to be an ideal green energy conversion device but their widespread applications are limited by the high price of the Pt-based catalysts and the instability in terms of surface CO toxicity in long-term ***,the PtFe alloy nanoparticles(NPs) with small particle size(~4.12 nm) supported on carbon black catalysts with different Pt/Fe atomic ratios(Pt_(1)Fe_(2)/C,Pt_(3)Fe_(4)/C,Pt_(1)Fe_(1)/C,and Pt_(2)Fe_(1)/C) are successfully prepared for enhanced anti-CO poisoning during methanol oxidation reaction(MOR).The optimal atomic ratio of Pt/Fe for the MOR is 1:2,and the mass activity of Pt_(1)Fe_(2)/C(5.40 A mg_(Pt)^(-1)) is 13.5 times higher than that of conventional commercial Pt/C(Pt/C-JM)(0.40 A mg_(Pt)^(-1)).The introduction of Fe into the Pt lattice forms the PtFe alloy phase,and the electron density of Pt is reduced after forming the PtFe ***-situ Fourier transform infrared results indicate that the addition of oxyphilic metal Fe has reduced the adsorption of reactant molecules on Pt during the *** doping of Fe atoms helps to desorb toxic intermediates and regenerate Pt active sites,promoting the cleavage of C-O bonds with good selectivity of CO_(2)(58.1%).Moreover,the Pt_(1)Fe_(2)/C catalyst exhibits higher CO tolerance,methanol electrooxidation activity,and long-term stability than other Pt_(x)Fe_(y)/C catalysts.

关键词： Alloy catalyst PtFe Methanol oxidation In-situ FTIR CO resistance

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Multifunctional nano-herb based on tumor microenvironment for enhanced tumor therapy of gambogic acid

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Chinese Chemical Letters 2024年第5期35卷 307-313页

作者： fengyun li Zerong pei Shuting Chen Gen li Mengyang liu liqin Ding Jingbo liu feng Qiu School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China College of Horticulture and Landscape Architecture Tianjin Agricultural UniversityTianjin 300384China State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Multifunctional drug delivery systems(DDSs)have shown great prospects in overcoming the heterogeneous barrier of delivery drugs to the complex tumor microenvironment(TME).In this study,multifunctional AS/Ge-pNAB microgels with dual-active targeting,triple environment responsiveness,and fluorescence imaging capability were prepared through a straightforward *** was aimed to improve the antitumor therapeutic application of gambogic acid(GA)based on the biological characteristics of *** microgels have a uniform double-layer structure with aptamer in the outer layer which helps in recognizing receptors on the tumor *** GA loaded nano-herb exhibited environment-responsive drug release profiles under acidic pH,reductant and high *** nano-herb significantly improved the accumulation of GA in tumor sites through the synergistic combination of the enhanced permeability and retention effect and dual-ligand mediated ***,it accelerated intracellular drug release and killed tumor ***,the nano-herb had specific therapeutic effects on the tumor in vitro and in vivo as they remarkably inhibited tumor growth while depicting optimal biosafety and lower levels of off-target ***,these findings demonstrate the great potential of the multifunctional AS/Ge-pNAB microgels for precisely targeted GA delivery and open a new avenue for the facile preparation of multifunctional DDSs.

关键词： Tumor microenvironment Microgels Gambogic acid Dual-active targeting Triple environment responsiveness Silver nanoclusters

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Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids

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Journal of Pharmaceutical Analysis 2024年第3期14卷 295-307页

作者： Xiao-feng Huang Ying Xue li Yong Tian-Tian Wang pei Luo lin-Sen Qing Chengdu Institute of Biology Chinese Academy of SciencesChengdu610041China State Key Laboratory for Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Sichuan Center for Disease Control and Prevention Chengdu610041China University of Chinese Academy of Sciences Beijing100049China

Triterpenoids widely exist in nature,displaying a variety of pharmacological *** triterpenoids in different matrices,especially in biological samples holds great ***-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical ***,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical ***,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass ***,routine HPLC analysis suffers from poor *** derivatization emerges as an indispensable technique in HPLC analysis to enhance its *** the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rhodamines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of *** review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of ***,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

关键词： Triterpenoid HPLC Derivatization Quantification

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Whole-genome sequencing in medicinal plants:current progress and prospect

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Science China(life Sciences) 2024年第2期67卷 258-273页

作者： Yifei pei liang Leng Wei Sun Baocai liu Xue feng Xiwen li Shilin Chen Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Institute of Herbgenomics Chengdu University of Traditional Chinese MedicineChengdu 611137China Innovative Institute of Chinese Medicine and Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Institute of Agricultural Bioresource Fujian Academy of Agricultural SciencesFuzhou 350003China

Advancements in genomics have dramatically accelerated the research on medicinal plants,and the development of herbgenomics has promoted the“Project of 1K Medicinal Plant Genome”to decipher their genetic ***,it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic *** genomes of 123 medicinal plants were published until September *** published genome sequences were investigated in this review,covering their classification,research teams,ploidy,medicinal functions,and sequencing *** than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant *** species account for a majority of sequenced medicinal *** whole genomes of plants in the Poaceae family are the most *** 40%of the published papers studied species with tonifying,replenishing,and heat-cleaning medicinal *** plants are still in the process of domestication as compared with crops,thereby resulting in unclear genetic backgrounds and the lack of pure lines,thus making their genomes more difficult to *** addition,there is still no clear routine framework for a medicinal plant to obtain a high-quality whole ***,a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal ***,whole genome-based biological studies of medicinal plants,including breeding and biosynthesis,were *** also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

关键词： herbgenomics whole genome high throughput sequencing research strategy model species application

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