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Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy

Acta Pharmaceutica Sinica B 2023年第4期13卷 1429-1437页

作者： Kamila Butowska Xuexiang Han ningqiang gong Rakan El-Mayta Rebecca MHaley Lulu Xue Wenqun Zhong Wei Guo Karin Wang Michael J.Mitchell Department of Bioengineering University of PennsylvaniaPhiladelphiaPA 19104USA Intercollegiate Faculty of Biotechnology University of Gdańsk&Medical University of GdańskGdańsk 80-307Poland Department of Biology University of PennsylvaniaPhiladelphiaPA 19104USA Department of Bioengineering Temple UniversityPhiladelphiaPA 19122USA Abramson Cancer Center Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Immunology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Cardiovascular Institute Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Regenerative Medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Evasion of apoptosis is a hallmark of cancer,attributed in part to overexpression of the antiapoptotic protein B-cell lymphoma 2(Bcl-2).In a variety of cancer types,including lymphoma,Bcl-2 is overexpressed.Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy.Therefore,the development of co-delivery systems for Bcl-2 targeting agents,such as small interfering RNA(siRNA),and chemotherapeutics,such as doxorubicin(DOX),holds promise for enabling combination cancer therapies.Lipid nanoparticles(LNPs)are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and delivery.Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs,here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNAloaded LNPs.Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts'lymphoma(Raji)cells,leading to effective inhibition of tumor growth in a mouse model of lymphoma.Based on these results,our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.

关键词： Lipid nanoparticles Doxorubicin Bcl-2 siRNA delivery Chemotherapy Lymphoma

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Effects of the physicochemical properties of gold nanostructures on cellular internalization

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Regenerative Biomaterials 2015年第4期2卷 273-280页

作者： ningqiang gong Shizhu Chen Shubin Jin Jinchao Zhang Paul C.Wang Xing-Jie Liang CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China Key Laboratory of Chemical Biology of Hebei Province Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationCollege of Chemistry and Environmental ScienceHebei UniversityBaoding 071002P.R.China Laboratory of Molecular Imaging Department of RadiologyHoward UniversityWashingtonDC 20060USA

Unique physicochemical properties of Au nanomaterials make them potential star materials in biomedicalapplications. However, we still know a little about the basic problem of what really mattersin fabrication of Au nanomaterials which can get into biological systems, especially cells, with highefficiency. An understanding of how the physicochemical properties of Au nanomaterials affecttheir cell internalization is of significant interest. Studies devoted to clarify the functions of variousproperties of Au nanostructures such as size, shape and kinds of surface characteristics in cell internalizationare under way. These fundamental investigations will give us a foundation for constructingAu nanomaterial-based biomedical devices in the future. In this review, we present the current advancesand rationales in study of the relationship between the physicochemical properties of Aunanomaterials and cell uptake. We also provide a perspective on the Au nanomaterial-cell interactionresearch.

关键词： gold nanostructures cellular internalization size,shape surface chemistry

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Natural and engineered bacterial outer membrane vesicles

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Biophysics Reports 2019年第4期5卷 184-198页

作者： Guangchao Qing ningqiang gong Xiaohui Chen Jing Chen Hong Zhang Yongchao Wang Ruifang Wang Shouwen Zhang Zhen Zhang Xianxian Zhao Yang Luo Xing-Jie Liang Department of Materials and Energy Southwest University Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Department of Clinical Laboratory Medicine Southwest Hospital Army Medical University University of Chinese Academy of Sciences Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular Implants College of Bioengineering Chongqing University Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province Department of Nuclear Medicinethe Affiliated Hospital Southwest Medical University West Essence Clinic Beijing Institute of Functional Neurosurgery&Xuanwu Hospital Capital Medical University

Bacterial outer membrane vesicle(OMV) is a kind of spherical lipid bilayer nanostructure naturally secreted by bacteria, which has diverse functions such as intracellular and extracellular communication,horizontal gene transfer, transfer of contents to host cells, and eliciting an immune response in host cells. In this review, several methods including ultracentrifugation and precipitation for isolating OMVs were summarized. The latest progresses of OMVs in biomedical fields, especially in vaccine development, cancer treatment, infection control, and bioimaging and detection were also summarized in this review. We highlighted the importance of genetic engineering for the safe and effective application and in facilitating the rapid development of OMVs. Finally, we discussed the bottleneck problems about OMVs in preparation and application at present and put forward our own suggestions about them.Some perspectives of OMVs in biomedical field were also provided.

关键词： Bacterial outer membrane vesicles (OMVs) Biogenesis Preparation Application

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Sparse Reconstructive Evidential Clustering for Multi-View Data

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 459-473页

作者： Chaoyu gong Yang You School of Computing National University of SingaporeSingapore

Although many multi-view clustering(MVC) algorithms with acceptable performances have been presented, to the best of our knowledge, nearly all of them need to be fed with the correct number of clusters. In addition, these existing algorithms create only the hard and fuzzy partitions for multi-view objects,which are often located in highly-overlapping areas of multi-view feature space. The adoption of hard and fuzzy partition ignores the ambiguity and uncertainty in the assignment of objects, likely leading to performance degradation. To address these issues, we propose a novel sparse reconstructive multi-view evidential clustering algorithm(SRMVEC). Based on a sparse reconstructive procedure, SRMVEC learns a shared affinity matrix across views, and maps multi-view objects to a 2-dimensional humanreadable chart by calculating 2 newly defined mathematical metrics for each object. From this chart, users can detect the number of clusters and select several objects existing in the dataset as cluster centers. Then, SRMVEC derives a credal partition under the framework of evidence theory, improving the fault tolerance of clustering. Ablation studies show the benefits of adopting the sparse reconstructive procedure and evidence theory. Besides,SRMVEC delivers effectiveness on benchmark datasets by outperforming some state-of-the-art methods.

关键词： Evidence theory multi-view clustering(MVC) optimization sparse reconstruction

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Exploring a Promising Region and Enhancing Decision Space Diversity for Multimodal Multi-Objective Optimization

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Tsinghua Science and Technology 2024年第2期29卷 325-342页

作者： Fei Ming Wenyin gong School of Computer Science China University of GeosciencesWuhan 430074China

During the past decade,research efforts have been gradually directed to the widely existing yet less noticed multimodal multi-objective optimization problems(MMOPs)in the multi-objective optimization community.Recently,researchers have begun to investigate enhancing the decision space diversity and preserving valuable dominated solutions to overcome the shortage caused by a preference for objective space convergence.However,many existing methods still have limitations,such as giving unduly high priorities to convergence and insufficient ability to enhance decision space diversity.To overcome these shortcomings,this article aims to explore a promising region(PR)and enhance the decision space diversity for handling MMOPs.Unlike traditional methods,we propose the use of non-dominated solutions to determine a limited region in the PR in the decision space,where the Pareto sets(PSs)are included,and explore this region to assist in solving MMOPs.Furthermore,we develop a novel neighbor distance measure that is more suitable for the complex geometry of PSs in the decision space than the crowding distance.Based on the above methods,we propose a novel dual-population-based coevolutionary algorithm.Experimental studies on three benchmark test suites demonstrates that our proposed methods can achieve promising performance and versatility on different MMOPs.The effectiveness of the proposed neighbor distance has also been justified through comparisons with crowding distance methods.

关键词： multimodal multi-objective optimization evolutionary algorithms promising region neighbor distance decision space coevolution

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Metagenomics reveals the microbial community and functional metabolism variation in the partial nitritation-anammox process:From collapse to recovery

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Journal of Environmental Sciences 2024年第1期135卷 210-221页

作者： Hong Wang Hui gong Xiaohu Dai Min Yang State Key Laboratory of Pollution Control and Resource Reuse College of Environmental Science and EngineeringTongji UniversityShanghai 200092China BIOMATH Department of Data Analysis and Mathematical ModellingGhent UniversityGhent 9000Belgium

Mainstream partial nitritation-anammox(PNA)process easily suffers from performance instability and even reactor collapse in application.Thus,it is of great significance to unveil the characteristic of performance recovery,understand the intrinsic mechanism and then propose operational strategy.In this study,we combined long-term reactor operation,batch tests,and metagenomics to reveal the succession of microbial community and functional metabolism variation from system collapse to recovery.Proper aeration control(0.10-0.25mg O_(2)/L)was critical for performance recovery.It was also found that Candidatus Brocadia became the dominant flora and its abundance increased from 3.5%to 11.0%.Significant enhancements in carbon metabolism and phospholipid biosynthesis were observed during system recovery,and the genes abundance related to signal transduction was dramatically increased.The up-regulation of sdh and suc genes showed the processes of succinate dehydrogenation and succinyl-CoA synthesis might stimulate the production of amino acids and the synthesis of proteins,thereby possibly improving the activity and abundance of AnAOB,which was conducive to the performance recovery.Moreover,the increase in abundance of hzs and hdh genes suggested the enhancement of the anammox process.Changes in the abundance of key genes involved in nitrogen metabolism indicated that nitrogen removal pathway was more diverse after system recovery.The achievement of performance recovery was driven by anammox,nitrification and denitrification coupled with dissimilatory nitrate reduction to ammonium.These results provide deeper insights into the recovery mechanism of PNA system and also provide a potential regulation strategy for the stable operation of the mainstream PNA process.

关键词： Partial nitritation-anammox Metagenomics Microbial community Functional metabolism Recovery

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Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2018-2037页

作者： Li Wang Wei-Hua gong Department of Emergency The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Surgery The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310052Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 60%of GC are linked to infection with Helicobacter pylori(H.pylori),a gram-negative,active,microaerophilic,and helical bacterium.This parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane proteins.Ferroptosis,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between H.pylori infection-related GC and ferroptosis.AIM To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.METHODS Gene expression profiles of GC patients and those with H.pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)databases.The FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox regression.The predictive ability of the FRGPI was validated in the GEO cohort.Finally,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.RESULTS Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and H.pylori-associated GC.The FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group.The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression.Moreover,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI cohort.The hub genes were also confirmed to be highly overexpressed in GC cell line

关键词： Ferroptosis Gastric cancer Helicobacter pylori infection Immune checkpoint protein Prognostic model Ferroptosis-related gene prognostic index

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Interplant communication:an emerging battlefield in plant-aphid-virus interactions

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Science China(Life Sciences) 2024年第5期67卷 1069-1071页

作者： Yunjing Wang Qian gong Yule Liu MOE Key Laboratory of Bioinformatics and Center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Beijing 100084China

Plants constantly face threats from various organisms,including pathogens and herbivores.Among the pathogens,plant viruses are obligate intracellular parasites that infect plants and cause serious crop yield losses.

关键词： plant Plants communication

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Even Search in a Promising Region for Constrained Multi-Objective Optimization

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 474-486页

作者： Fei Ming Wenyin gong Yaochu Jin School of Computer Science China University of GeosciencesWuhan 430074China IEEE Faculty of Technology Bielefeld UniversityNorth Rhine-Westphalia 33619Germany School of Engineering Westlake UniversityHangzhou 310030China

In recent years, a large number of approaches to constrained multi-objective optimization problems(CMOPs) have been proposed, focusing on developing tweaked strategies and techniques for handling constraints. However, an overly finetuned strategy or technique might overfit some problem types,resulting in a lack of versatility. In this article, we propose a generic search strategy that performs an even search in a promising region. The promising region, determined by obtained feasible non-dominated solutions, possesses two general properties.First, the constrained Pareto front(CPF) is included in the promising region. Second, as the number of feasible solutions increases or the convergence performance(i.e., approximation to the CPF) of these solutions improves, the promising region shrinks. Then we develop a new strategy named even search,which utilizes the non-dominated solutions to accelerate convergence and escape from local optima, and the feasible solutions under a constraint relaxation condition to exploit and detect feasible regions. Finally, a diversity measure is adopted to make sure that the individuals in the population evenly cover the valuable areas in the promising region. Experimental results on 45 instances from four benchmark test suites and 14 real-world CMOPs have demonstrated that searching evenly in the promising region can achieve competitive performance and excellent versatility compared to 11 most state-of-the-art methods tailored for CMOPs.

关键词： Constrained multi-objective optimization even search evolutionary algorithms promising region real-world problems

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Integrative regulatory mechanisms of stomatal movements under changing climate

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Journal of Integrative Plant Biology 2024年第3期66卷 368-393页

作者： Jingbo Zhang Xuexue Chen Yajing Song Zhizhong gong State Key Laboratory of Nutrient Use and Management College of Resources and Environmental SciencesNational Academy of Agriculture Green DevelopmentChina Agricultural UniversityBeijing 100193China State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Plant Environmental Resilience College of Biological SciencesChina Agricultural UniversityBeijing 100094China Institute of Life Science and Green Development School of Life SciencesHebei UniversityBaoding 071001China

Global climate change-caused drought stress,high temperatures and other extreme weather profoundly impact plant growth and development,restricting sustainable crop production.To cope with various environmental stimuli,plants can optimize the opening and closing of stomata to balance CO_(2)uptake for photosynthesis and water loss from leaves.Guard cells perceive and integrate various signals to adjust stomatal pores through turgor pressure regulation.Molecular mechanisms and signaling networks underlying the stomatal movements in response to environmental stresses have been extensively studied and elucidated.This review focuses on the molecular mechanisms of stomatal movements mediated by abscisic acid,light,CO_(2),reactive oxygen species,pathogens,temperature,and other phytohormones.We discussed the significance of elucidating the integrative mechanisms that regulate stomatal movements in helping design smart crops with enhanced water use efficiency and resilience in a climate-changing world.

关键词： environmental stress guard cell plant regulatory mechanisms stomatal movements

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