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A Dynamic Covalent Bonding-based nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect

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Chinese Journal of Polymer Science 2024年第5期42卷 559-569,I0005页

作者： sai-nan liu Jia-Hui Meng Li-Yun Cui Hua Chen Lin-Qi Shi Ru-Jiang Ma Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer ChemistryTianjin Key Laboratory of Functional Polymer MaterialsState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Efficient intracellular delivery of protein drugs is critical for protein therapy.The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect.However,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties.Herein,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,PEG-b-P(Asp-co-AspDA)and PAE-b-P(Asp-co-AspPBA),and two 2-acetylphenylboronic acid(2-APBA)-functionalized drugs,2-APBA-RNase A and 2-APBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNPs)via dynamic phenylboronic acid(PBA)-catechol bond between PBA and dopamine(DA)moieties.The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior.Under the slight acidic environment at tumor tissue,RNase A/DOX@MNPs are positively charged,promoting their endocytosis.Upon cellular uptake into endosome,further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs.In cytoplasm,the high level of GSH removed the modification of 2-APBA on drugs.The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect.This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.

关键词： Drug co-delivery Combination therapy Dynamic covalent bond

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Recent advances in the culture-independent discovery of natural products using metagenomic approaches

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Chinese Journal of Natural Medicines 2024年第2期22卷 100-111页

作者： SHEN Yiping liu nan WANG Zongqiang Laboratory of Microbial Drug Discovery China Pharmaceutical UniversityNanjing 211198China

Natural products derived from bacterial sources have long been pivotal in the discovery of drug leads.However,the cultivation of only about 1%of bacteria in laboratory settings has left a significant portion of biosynthetic diversity hidden within the genomes of uncultured bacteria.Advances in sequencing technologies now enable the exploration of genetic material from these metagenomes through culture-independent methods.This approach involves extracting genetic sequences from environmental DNA and applying a hybrid methodology that combines functional screening,sequence tag-based homology screening,and bioinformatic-assisted chemical synthesis.Through this process,numerous valuable natural products have been identified and synthesized from previously uncharted metagenomic territories.This paper provides an overview of the recent advancements in the utilization of culture-independent techniques for the discovery of novel biosynthetic gene clusters and bioactive small molecules within metagenomic libraries.

关键词： Metagenomics Culture-independent approach Natural product Functional screening Sequence tag-based homology screening Syn-BNP

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Identification of an odorant receptor responding to sex pheromones in Spodoptera frugiperda extends the novel type-I PR lineage in moths

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Insect Science 2024年第2期31卷 489-502页

作者： sai Zhang Emmanuelle Jacquin-Joly Nicolas Montagne Fang liu Yang liu Guirong Wang College of Horticulture and Plant Protection Yangzhou UniversityYangzhouChina State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBejingChina Institute of Ecology and En vironmental Sciences of Paris INRAESorbonne UniversityCNRSIRDUPECUniversity of ParisVersaillesFrance Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina

moths,pheromone receptors(PRs)are crucial for intraspecific sexual communication between males and females.Moth PRs are considered as an ideal model for studying the evolution of insect PRs,and a large number of PRs have been identified and functionally characterized in different moth species.Moth PRs were initially thought to fall into a single monophyletic clade in the odorant receptor(OR)family,but recent studies have shown that ORs in another lineage also bind type-I sex pheromones,which indicates that type-I PRs have multiple independent origins in the Lepidoptera.In this study,we investigated whether ORs of the pest moth Spodoptera frugiperda belonging to clades closely related to this novel PR lineage may also have the capacity to bind type-I pheromones and serve as male PRs.Among the 7 ORs tested,only 1(SfruOR23)exhibited a male-biased expression pattern.Importantly,in vitro functional characterization showed that SfruOR23 could bind several type-I sex pheromone compounds with Z-9-tetradecenal(Z9-14:Ald),a minor component found in female sex pheromone glands,as the optimal ligand.In addition,SfruOR23 also showed weak responses to plant volatile organic compounds.Altogether,we characterized an S.frugiperda PR positioned in a lineage closely related to the novel PR clade,indicating that the type-I PR lineage can be extended in moths.

关键词： odorant receptor pheromone receptor lineage sex pheromone Spodoptera frugiperda

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High Dynamic Bounding and Jumping Motion of Quadruped Robot Based on Stable Optimization Control

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Journal of Bionic Engineering 2024年第1期21卷 101-111页

作者： sai Gu Fei Meng Botao liu Junyao Gao Qiang Huang School of Mechatronical Engineering Beijing Institute of Technology100081 BeijingChina Key Laboratory of Biomimetic Robots and Systems Ministry of EducationBeijing 100081China

Aiming at the environment such as ravines and obstacles that may be encountered in the actual movement,this paper proposes a method for optimizing the bounding and jumping motion based on the ground touching force trajectory and the air motion trajectory of the quadruped robot.The method of optimizing the ground reaction force according to the speed of the demand and the height of the jump,and adjusting the stance and swing time according to the relationship of dynamics and momentum conservation.At the same time,under the constraints of dynamics and energy consumption of the robot system,considering the jumping distance and height,a method for optimizing the air trajectory of bounding and jumping is proposed.State switching and landing stability control are also added.Finally,the experimental results show that the quadruped robot has strong bounding and jumping ability,and has achieved stable bounding movement and forward jump movement of 0.8 m.

关键词： Quadruped robot High dynamic motion control-Periodic limit cycle Trajectory optimization

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A Task Scheduling Algorithm Based on Clustering Pre-processing in Space-Based Information Network

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Chinese Journal of Electronics 2024年第1期33卷 217-230页

作者： Yufei WANG Jun liu Shengnan ZHANG sai XU Jingyi WANG School of Computer Science and Engineering Northeastern University

With the diversification of space-based information network task requirements and the dramatic increase in demand, the efficient scheduling of various tasks in space-based information network becomes a new challenge. To address the problems of a limited number of resources and resource heterogeneity in the space-based information network, we propose a bilateral pre-processing model for tasks and resources in the scheduling pre-processing stage. We use an improved fuzzy clustering method to cluster tasks and resources and design coding rules and matching methods to match similar categories to improve the clustering effect. We propose a space-based information network task scheduling strategy based on an ant colony simulated annealing algorithm for the problems of high latency of space-based information network communication and high resource dynamics. The strategy can efficiently complete the task and resource matching and improve the task scheduling performance. The experimental results show that our proposed task scheduling strategy has less task execution time and higher resource utilization than other algorithms under the same experimental conditions. It has significantly improved scheduling performance.

关键词： Space-based information network Task scheduling Resource clustering Ant colony optimization Simulated annealing

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Artificial intelligence for the detection of glaucoma with SD-OCT images:a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 408-419页

作者： nan-nan Shi Jing Li Guang-Hui liu Ming-Fang Cao Department of Ophthalmology Affiliated People’s Hospital(Fujian Provincial People’s Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina Eye Institute of Integrated Chinese and Western Medicine Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina

●AIM:To quantify the performance of artificial intelligence(AI)in detecting glaucoma with spectral-domain optical coherence tomography(SD-OCT)images.●METHODS:Electronic databases including PubMed,Embase,Scopus,ScienceDirect,ProQuest and Cochrane Library were searched before May 31,2023 which adopted AI for glaucoma detection with SD-OCT images.All pieces of the literature were screened and extracted by two investigators.Meta-analysis,Meta-regression,subgroup,and publication of bias were conducted by Stata16.0.The risk of bias assessment was performed in Revman5.4 using the QUADAS-2 tool.●RESULTS:Twenty studies and 51 models were selected for systematic review and Meta-analysis.The pooled sensitivity and specificity were 0.91(95%CI:0.86–0.94,I2=94.67%),0.90(95%CI:0.87–0.92,I2=89.24%).The pooled positive likelihood ratio(PLR)and negative likelihood ratio(NLR)were 8.79(95%CI:6.93–11.15,I2=89.31%)and 0.11(95%CI:0.07–0.16,I2=95.25%).The pooled diagnostic odds ratio(DOR)and area under curve(AUC)were 83.58(95%CI:47.15–148.15,I2=100%)and 0.95(95%CI:0.93–0.97).There was no threshold effect(Spearman correlation coefficient=0.22,P>0.05).●CONCLUSION:There is a high accuracy for the detection of glaucoma with AI with SD-OCT images.The application of AI-based algorithms allows together with“doctor+artificial intelligence”to improve the diagnosis of glaucoma.

关键词： artificial intelligence spectral-domain optical coherence tomography glaucoma Meta-analysis

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Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine

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Cancer Pathogenesis and Therapy 2024年第2期2卷 112-120页

作者： sai Huang Peng Chen Lu Wang Lingmin Xu nan Wang Fei Li Liping Dou Daihong liu Department of Hematology Senior Department of HematologyThe Fifth Medical Center of PLA General HospitalBejing 100039China National Clinical Research Center of Geriatric Diseases Chinese PLA General HospitalBejing 100853China Chinese PLA Medical School Beijing 100853China Department of Hematology The First Medical Center of PLA General HospitalBejing 100853China

Background:Acute myeloid leukemia(AML)is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers.Decitabine,a deoxyribonucleic acid(DNA)methyltransferase(DNMT)in-hibitor,combined with cytarabine,aclarubicin hydrochloride,and granulocyte colony-stimulating factor(DCAG),has been used in patients newly diagnosed with AML.This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities,as well as those with specific gene mutations.However,the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined.Therefore,this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.Methods:This study analyzed the clinical data and genetic mutations based on next-generation sequencing(NGS)in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army(PLA)General Hospital from January 2008 to August 2020.Factors associated with the cumulative incidence of relapse(CIR)and leukemia-free survival(LFS)in patients newly diagnosed with AML were analyzed.Results:The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD,KIT,PTPN11,GATA2,or IDH1 mutations during univariable analysis,whereas PTPN11 mutation was solely significant in multivariable analysis,with an increased likelihood of CIR(P=0.001)and reduced LFS duration(P=0.077).Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk(P=0.044)and decreased LFS duration(P=0.042)in multivariable analysis.In this study,we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.Conclusion:NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations,indicating the need for new therapies that target this high-risk subtype of AML.These results offer a po

关键词： Acute myeloid leukemia Next-generation sequencing Prognosis DNA methyltransferase Chemotherapy

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Recent progress on rapid diagnosis of COVID-19 by point-of-care testing platforms

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Chinese Chemical Letters 2024年第3期35卷 66-75页

作者： Ya-nan Tang Dingding Jiang Xuejun Wang Yunqi liu Dacheng Wei State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200433China Institute of Molecular Materials and Devices Fudan UniversityShanghai 200433China

The outbreak of COVID-19 has drawn great attention around the world.SARS-CoV-2 is a highly infectious virus with occult transmission by many mutations and a long incubation period.In particular,the emergence of asymptomatic infections has made the epidemic even more severe.Therefore,early diagnosis and timely management of suspected cases are essential measures to control the spread of the virus.Developing simple,portable,and accurate diagnostic techniques for SARS-CoV-2 is the key to epidemic prevention.The advantages of point-of-care testing technology make it play an increasingly important role in viral detection and screening.This review summarizes the point-of-care testing platforms developed by nucleic acid detection,immunological detection,and nanomaterial-based biosensors detection.Furthermore,this paper provides a prospect for designing future highly accurate,cheap,and convenient SARS-CoV-2 diagnostic technology.

关键词： COVID-19 Point-of-care testing platforms Nucleic acid detection Asymptomatic infection Biosensors

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Molecular phylogenetic relationships based on mitochondrial genomes of novel deep-sea corals(Octocorallia:Alcyonacea):Insights into slow evolution and adaptation to extreme deep-sea environments

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Zoological Research 2024年第1期45卷 215-225页

作者： Zhan-Fei Wei Kai-Wen Ta nan-nan Zhang Shan-Shan liu Liang Meng Kai-Qiang liu Chong-Yang Cai Xiao-Tong Peng Chang-Wei Shao National Key Laboratory of Mariculture Biobreeding and Sustainable Goods Yellow Sea Fisheries Research InstituteChinese Academy of Fishery SciencesQingdaoShandong 266071China BGI-Qingdao BGI-ShenzhenQingdaoShandong 266555China Institute of Deep-Sea Science and Engineering Chinese Academy of SciencesSanyaHainan 572000China

A total of 10 specimens of Alcyonacea corals were collected at depths ranging from 905 m to 1633 m by the manned submersible Shenhai Yongshi during two cruises in the South China Sea(SCS).Based on mitochondrial genomic characteristics,morphological examination,and sclerite scanning electron microscopy,the samples were categorized into four suborders(Calcaxonia,Holaxonia,Scleraxonia,and Stolonifera),and identified as 9 possible new cold-water coral species.Assessments of GC-skew dissimilarity,phylogenetic distance,and average nucleotide identity(ANI)revealed a slow evolutionary rate for the octocoral mitochondrial sequences.The nonsynonymous(Ka)to synonymous(Ks)substitution ratio(Ka/Ks)suggested that the 14 protein-coding genes(PCGs)were under purifying selection,likely due to specific deep-sea environmental pressures.Correlation analysis of the median Ka/Ks values of five gene families and environmental factors indicated that the genes encoding cytochrome b(cyt b)and DNA mismatch repair protein(mutS)may be influenced by environmental factors in the context of deep-sea species formation.This study highlights the slow evolutionary pace and adaptive mechanisms of deep-sea corals.

关键词： Mitochondrial genome Alcyonacea Ka/Ks evolution Environmental factors

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A hybrid attention model based on first-order statistical features for smoke recognition

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Science China(Technological Sciences) 2024年第3期67卷 809-822页

作者： GUO nan liu JiaHui DI KeXin GU Ke QIAO JunFei Beijing Laboratory of Smart Environmental Protection Beijing Key Laboratory of Computational Intelligence and Intelligent SystemBeijing Artificial Intelligence InstituteBeijing 100124China Faculty of Information Technology Beijing University of TechnologyBeijing 100124China

Smoke and fire recognition are of great importance on foreseeing fire disasters and preventing environmental pollution by monitoring the burning process of objects(e.g., straw, fuels). However, since fire images suffer from problems like the variability of the features, complexity of scenarios, interference from background, changeable weather conditions as well as image quality problems, identifying smoke and fire accurately and promptly from a given image still remains a substantial challenge. Automatically learning the features of smoke images by CNNs has improved the target recognition ability compared to traditional approaches,nonetheless, convolutions and pooling operations in CNNs may cause severe information loss which may lead to misjudgment.To tackle the above problems, this paper proposed a hybrid attention model based on the characteristics of smoke images. This model adopted multiple optimized attention mechanism in several stages to quickly and precisely capture the important features,achieving state-of-the-art performance on smoke and fire recognition in terms of accuracy and speed. Our proposed module mainly consists of two stages: pooling and attention. In the first stage, we conducted several newly proposed first-order pooling methods. Through traversing the data space in a larger scope, features are better reserved, thus constructing a more intact feature space of smoke and fire in an image. In the second stage, feature maps are aggregated together to perform channel and spatial attention. The channel and spatial dependencies allow us to quickly catch the important features presented in an image. By fully exploring the feature space and prominent salient features, characteristics of smoke and fire are better presented so as to obtain better smoke and fire detection results. Experiments have been conducted on public smoke detection dataset and new proposed fine-grained smoke and fire detection database. Experimental results revealed that the proposed method outperformed popular deep CNNs and exis

关键词： hybrid attention first-order pooling smoke and fire detection deep convolutional neural networks

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