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Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

Bioactive Materials 2022年第11期7卷 300-319页

作者： Shuyan Han Jun Wu School of Biomedical Engineering Sun Yat-sen UniversityShenzhen518057China

Though increasing understanding and remarkable clinical successes have been made, enormous challenges remain to be solved in the field of cancer immunotherapy. In this context, biomaterial-based immunomodulatory strategies are being developed to boost antitumor immunity. For the local immunotherapy, macroscale bioma-terial scaffolds with 3D network structures show great superiority in the following aspects: facilitating the encapsulation, localized delivery, and controlled release of immunotherapeutic agents and even immunocytes for more efficient immunomodulation. The concentrating immunomodulation in situ could minimize systemic tox-icities, but still exert abscopal effects to harness the power of overall anticancer immune response for eradicating malignancy. To promote such promising immunotherapies, the design requirements of macroscale 3D scaffolds should comprehensively consider their physicochemical and biological properties, such as porosity, stiffness, surface modification, cargo release kinetics, biocompatibility, biodegradability, and delivery modes. To date, increasing studies have focused on the relationships between these parameters and the biosystems which will guide/assist the 3D biomaterial scaffolds to achieve the desired immunotherapeutic outcomes. In this review, by highlighting some recent achievements, we summarized the latest advances in the development of various 3D scaffolds as niches for cancer immunotherapy. We also discussed opportunities, challenges, current trends, and future perspectives in 3D macroscale biomaterial scaffold-assisted local treatment strategies. More importantly, this review put more efforts to illustrate how the 3D biomaterial systems affect to modulate antitumor immune activities, where we discussed how significant the roles and behaviours of 3D macroscale scaffolds towards in situ cancer immunotherapy in order to direct the design of 3D immunotherapeutic.

关键词： Three-dimensional(3D) Macroscale Hydrogels Scaffolds Cancer immunotherapy

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Facile and One-step Direct Synthesis of Poly(valine)as a Robust Drug Nanocarrier for Enhanced Breast Cancer Therapy

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Chinese Journal of Polymer Science 2022年第9期40卷 1016-1027页

作者： Ya-Bin Meng Jun Wu School of Biomedical Engineering Sun Yat-sen UniversityShenzhen 518107China

Synthetic poly(amino acid)s with good biodegradable and biocompatible properties have attracted increased attention as carriers in biomedical applications in recent years,their synthesis and purification procedures are usually complicated and some by-products would occur yet.Given this,polypeptide with good biodegradable and biocompatible properties is prepared and optimized by one-step and direct synthesis strategy and poly(valine)(PVal)is selected here as a model polypeptide in this study.This newly generated PVal can self-assemble into poly(valine)nanoparticles(PVal-NPs)with a high drug-loading capacity(>20 wt%)of doxorubicin(DOX)and shows strong cytotoxicity against 4T1 cells.Upon cellular internalization,the release of DOX could be accelerated by the endosomal acidic environment which leads to enhanced anticancer effects.The results in vivo show that DOX@PVal-NPs have a long blood circulation time,high cancer accumulation and penetration,and good therapeutic performance in 4T1 tumor-bearing mice without causing obvious adverse effect on main organs.With these combined advantages,these PVal-based nanoplatform would provide an effective drug delivery tool for clinical breast cancer therapy.

关键词： Poly(amino acid) Nanoparticle Drug carrier Doxorubicin Breast cancer

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Local Stability to the Einstein-Euler System in Schwarzschild Space-time

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Acta Mathematicae Applicatae Sinica 2022年第2期38卷 352-367页

作者： Jun Wu Bo-ling GUO Institute of Applied Physics and Computational Mathematics Beijing 100088China

We study the Schwarzschild spacetime solutions to the Einstein-Euler equations.In our analysis,we aim to show local stability under small perturbations.To resolve this problem,we use the Nash-Moser(-Hamilton)theorem.T... 详细信息

关键词： schwarzschild metric local stability Nash-Moser(-Hamilton)theorem

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New concepts for generating interspecies chimeras using human pluripotent stem cells

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Protein & Cell 2022年第4期13卷 234-238页

作者： Alejandro De Los Angeles Jun Wu Department of Psychiatry Yale University School of MedicineNew HavenCTUSA Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA

The worldwide paucity of transplantable organs for patients is a devastating problem.While different approaches have been conceived to address this donor organ shortage,one strategy that has garnered significant attention recently is the prospect of producing human organs in animals through a technique called interspecies blastocyst complementation based on the generation of interspecies chimeras.Interspecies blastocyst complementation works by injecting pluripotent stem(PS)cells from one species into organogenesis-disabled blastocysts of another species(Kobayashi et al.,2010).As the chimeric embryo develops,donor cells can fill the vacated developmental organ niche and enrich in a target organ of interest.In principle,interspecies blastocyst complementation may one day allow the generation of human organs inside animals.However,some ethical issues concerning research and potential human clinical use with chimeras persist(Hyun,2019).

关键词： organs donor generating

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A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds

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Nano Research 2023年第1期16卷 905-916页

作者： Zejun Xu Guiting Liu Li Zheng Jun Wu The State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration Life Science InstitutesGuangxi Medical UniversityNanning 530021China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong Kong 999077China

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients.Therefore,a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds.In this study,chitosan methacrylate-gallic acid(CSMA-GA)polymer with antioxidant activity,antimicrobial activity,and ultraviolet(UV)-triggered gelling properties was developed as a hydrogel precursor.Meanwhile,amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle(NP)with strong antibacterial activity.Subsequently,F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity.The hybrid hydrogel platform(CSMA-GA/F127/chlorhexidine(CMGFC))exhibited high antibacterial efficiency(>99.9%)and strong reactive oxygen species(ROS)scavenging ability(>80.0%),which effectively protected cells from external oxidative stress(upregulated superoxide dismutase(SOD)and glutathione/oxidized glutathione disulfide(GSH/GSSG)levels and downregulated malondialdehyde(MDA)levels).Moreover,in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses(downregulated interleukin-6(IL-6)and upregulated interleukin-10(IL-10)levels),promoted angiogenesis(upregulated vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule-1(CD 31)levels),and wound healing(enhanced collagen deposition and tissue remodelling).Overall,the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.

关键词： antimicrobial antioxidant diabetic wound hydrogel

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Development of an onsite calibration device for robot manipulators

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Frontiers of Information Technology & Electronic Engineering 2023年第2期24卷 217-230页

作者： Ziwei WAN Chunlin ZHOU Haotian ZHANG Jun Wu College of Control Science and Engineering Zhejiang UniversityHangzhou310063China Huzhou Institute of Zhejiang University Huzhou313098China Binjiang Institute of Zhejiang University Hangzhou310014China School of Information and Software Engineering University of Electronic Science and Technology of ChinaChengdu610054China

A novel in-contact three-dimensional(3D)measuring device,called MultiCal,is proposed as a convenient,low-cost(less than US$5000),and robust facility for onsite kinematic calibration and online measurement of robot manipulator accuracy.The device hasμm-level accuracy and can be easily embedded in robot cells.During the calibration procedure,the robot manipulator first moves automatically to multiple end-effector orientations with its tool center point(TCP)constrained on a fixed point by a 3D displacement measuring device(single point constraint),and the corresponding joint angles are recorded.Then,the measuring device is precisely mounted at different positions using a well-designed fixture,and the above measurement process is repeated to implement a multi-point constraint.The relative mounting positions are accurately measured and used as prior information to improve calibration accuracy and robustness.The results of theoretical analysis indicate that MultiCal reduces calibration accuracy by 10%to 20%in contrast to traditional non-contact 3D or six-dimensional(6D)measuring devices(such as laser trackers)when subject to the same level of artificial measurement noise.The results of a calibration experiment conducted on a Staubli TX90 robot show that MultiCal has only 7%to 14%lower calibration accuracy compared to a measuring arm with a laser scanner,and 21%to 30%lower time efficiency compared to a 6D binocular vision measuring system,yielding maximum and mean absolute position errors of 0.831 mm and 0.339 mm,respectively.

关键词： Calibration device Kinematic calibration Onsite calibration Absolute accuracy

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A multi-point collaborative DDoS defense mechanism for IIoT environment

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Digital Communications and Networks 2023年第2期9卷 590-601页

作者： Hongcheng Huang Peixin Ye Min Hu Jun Wu School of Communication and Information Engineering Chongqing University of Posts and TelecommunicationsChongqing400065China Chongqing Engineering Research Center of Communication Software Chongqing400065China

Nowadays,a large number of intelligent devices involved in the Industrial Internet of Things(IIoT)environment are posing unprecedented cybersecurity challenges.Due to the limited budget for security protection,the IIoT devices are vulnerable and easily compromised to launch Distributed Denial-of-Service(DDoS)attacks,resulting in disastrous results.Unfortunately,considering the particularity of the IIoT environment,most of the defense solutions in traditional networks cannot be directly applied to IIoT with acceptable security performance.Therefore,in this work,we propose a multi-point collaborative defense mechanism against DDoS attacks for IIoT.Specifically,for the single point DDoS defense,we design an edge-centric mechanism termed EdgeDefense for the detection,identification,classification,and mitigation of DDoS attacks and the generation of defense information.For the practical multi-point scenario,we propose a collaborative defense model against DDoS attacks to securely share the defense information across the network through the blockchain.Besides,a fast defense information sharing mechanism is designed to reduce the delay of defense information sharing and provide a responsive cybersecurity guarantee.The simulation results indicate that the identification and classification performance of the two machine learning models designed for EdgeDefense are better than those of the state-of-the-art baseline models,and therefore EdgeDefense can defend against DDoS attacks effectively.The results also verify that the proposed fast sharing mechanism can reduce the propagation delay of the defense information blocks effectively,thereby improving the responsiveness of the multi-point collaborative DDoS defense.

关键词： Industrial internet of things(IIoT) DDoS Deep learning Blockchain Edge computing

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Aggregation-induced emission luminogens reveal cell cycle-dependent telomerase activity in cancer cells

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National Science Review 2021年第6期8卷 70-79页

作者： Xia wu Jun Wu jun Dai Biao Chen Zhe Chen Shixuan Wang Feng wu Xiaoding Lou Fan Xia Engineering Research Center of Nano-Geomaterials of Ministry of Education Faculty of Materials Science and ChemistryChina University of Geosciences Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

Telomerase acts as an important biomarker for tumor identification, and synthesizes telomeric repeats at the end of chromosome telomeres during the replicative phase of the cell cycle; thus, the expression level of telomerase changes as the cell cycle progresses. TERT m RNA expression and telomerase activity were significantly increased in over 80% of human cancers from tissue specimens. Although many efforts have been made in detecting the activity of TERT m RNA and active telomerase, the heterogeneous behavior of the cell cycle was overlooked, which might affect the accuracy of the detection results. Herein, the AIEgen-based biosensing systems of Py TPA-DNA and Silole-R were developed to detect the cellular level of TERT m RNA and telomerase in different cell cycles. As a result, the fluorescence signal of cancer cells gradually increased from G0/G1, G1/S to S phase. In contrast, both cancer cells arrested at G2/M phase and normal cells exhibited negligible fluorescence intensities. Compared to normal tissues, malignant tumor samples demonstrated a significant turn-on fluorescence signal. Furthermore, the transcriptomics profiling revealed that tumor biomarkers changed as the cell cycle progressed and biomarkers of CA9, TK1 and EGFR were more abundantly expressed at early S stage. In this vein, our study presented advanced biosensing tools for more accurate analysis of the cell-cycle-dependent activity of TERT m RNA and active telomerase in clinical tissue samples.

关键词： cell cycle TERT mRNA telomerase activity AIEgens biomarkers

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Residual index for measurement configuration optimization in robot kinematic calibration

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Science China(Technological Sciences) 2023年第7期66卷 1899-1915页

作者： YE Hao wu jun State Key Laboratory of Tribology in Advanced Equipment and Institute of Manufacturing Engineering Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Beijing Key Lab of Precision/Ultra-precision Manufacturing Equipment and Control Beijing 100084China

To improve the efficiency and accuracy of kinematic calibration,the selection of measurement configurations is an important issue.In previous research,optimal measurement configurations mainly are selected by maximizing observability indices.However,the traditional observability indices only focus on the identification efficiency of the error parameters,while the purpose of robot kinematic calibration is to improve accuracy.To solve the inconsistency of the purpose between the observability index and calibration,the concept of the residual index to represent the residual distribution of the end effector after robot kinematic calibration with the measurement noise is proposed.Based on the quadratic form minimization of residuals,this article defines a specific residual index,O^(r),which is dimensionless and strictly better with the increase of measurement configurations.The indices are used to select measurement configurations in the kinematic calibration of a 5-DOF 2UPU/SP-RR hybrid robot,and the calibration results show that the proposed residual index is better than the traditional indices in the accuracy and stability of the end effector residual.

关键词： residual index observability index kinematic calibration measurement configuration optimization

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Local regularity properties for ID mixed nonlinear Schrodinger equations on half-line

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Frontiers of Mathematics in China 2020年第6期15卷 1121-1142页

作者： Boling GUO Jun Wu Institute of Applied Physics and Computational Mathematics Beijing 100088China Graduate School of China Academy of Engineering Physics Beijing 100088China

The main purpose of this paper is to consider the initial-boundary value problem for the 1D mixed nonlinear Schrodinger equation ut=iαu_(xx)+βu^(2)u_(x)+γ|u|^(2)u_(x)+i|u|^(2)u on the half-line with inhomogeneous boundary condition.We combine Laplace transform method with restricted norm method to prove the local well-posedness and continuous dependence on initial and boundary data in low regularity Sobolev spaces.Moreover,we show that the nonlinear part of the solution on the half-line is smoother than the initial data.

关键词： Mixed nonlinear Schrodinger(MNLS)equations initial-boundary value problem(IBVP) Bourgain spaces local well-posedness

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