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Recombinant adeno-associated virus 8 vector in gene therapy:Opportunities and challenges

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Genes & Diseases 2024年第1期11卷 283-293页

作者： Liyuan Zhao Zixuan yang Minhui zheng Lei Shi Mengyun gu Gang Liu Feng Miao yan Chang Fanghua Huang Naping Tang Anhui University of Traditional Chinese Medicine HefeiAnhui 230000China yangtze Delta Drug Advanced Research Institute Yangtze Delta Pharmaceutical CollegeNantongJiangsu226133China Shanghai Innostar Bio-Technology Co. LtdChina State Institute of Pharmaceutical IndustryShanghai 201203China Innostar Bio-tech Nantong Co. Ltd.NantongJiangsu 226133China Center for Drug Evaluation National Medical Products AdministrationBeijing 100022China

In recent years,significant breakthroughs have been made in the field of gene ther-apy.Adeno-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of interest.Among the AAV vectors,AAV serotype 8(AAv8)has attracted much attention for its efficient and stable gene transfection into specific tissues.Currently,recombinant AAv8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.

关键词： AAV8 Adeno-associated virus Gene therapy Primates

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

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Neural Regeneration Research 2024年第8期19卷 1812-1821页

作者： Xinyang Zhou Yehua Lv Huimin Xie yan Li Chang Liu Mengru zheng Ronghua Wu Songlin Zhou Xiaosong gu Jingjing Li Daguo Mi Suzhou Medical College of Soochow University SuzhouJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Orthopedic Nantong Traditional Chinese Medicine HospitalNantongJiangsu ProvinceChina Nantong Stomatological Hospital Affiliated to Nantong University NantongJiangsu ProvinceChina Department of General Practice Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

关键词： ceRNA network exosomes fibroblast cells Gene Ontology(GO) Kyoto Encyclopedia of Genes and Genomes(KEGG) protein-protein interaction(PPI)networks RNA-seq Schwann cells

Classifying Chinese Medicine Constitution Using Multimodal Deep-Learning Model

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Chinese Journal of Integrative Medicine 2024年第2期30卷 163-170页

作者： gu Tian-yu yan Zhuang-zhi JIANG Jie-hui School of Communication&Information Engineering Shanghai UniversityShanghai(200444)China School of Life Science Shanghai UniversityShanghai(200444)China

Objective:To develop a multimodal deep-learning model for classifying Chinese medicine constitution,i.e.,the balanced and unbalanced constitutions,based on inspection of tongue and face images,pulse waves from palpation,and health information from a total of 540 subjects.Methods:This study data consisted of tongue and face images,pulse waves obtained by palpation,and health information,including personal information,life habits,medical history,and current symptoms,from 540 subjects(202 males and 338 females).Convolutional neural networks,recurrent neural networks,and fully connected neural networks were used to extract deep features from the data.Feature fusion and decision fusion models were constructed for the multimodal data.Results:The optimal models for tongue and face images,pulse waves and health information were ResNet18,Gate Recurrent Unit,and entity embedding,respectively.Feature fusion was superior to decision fusion.The multimodal analysis revealed that multimodal data compensated for the loss of information from a single mode,resulting in improved classification performance.Conclusions:Multimodal data fusion can supplement single model information and improve classification performance.Our research underscores the effectiveness of multimodal deep learning technology to identify body constitution for modernizing and improving the intelligent application of Chinese medicine.

关键词： Chinese medicine constitution classification multimodal deep learning tongue image face image pulsewave health information

High-Order Decoupled and Bound Preserving Local Discontinuous Galerkin Methods for a Class of Chemotaxis Models

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Communications on Applied Mathematics and Computation 2024年第1期6卷 372-398页

作者： Wei zheng yan Xu School of Mathematical Sciences University of Science and Technology of ChinaHefei230026AnhuiChina

In this paper,we explore bound preserving and high-order accurate local discontinuous Galerkin(LDG)schemes to solve a class of chemotaxis models,including the classical Keller-Segel(KS)model and two other density-dependent problems.We use the convex splitting method,the variant energy quadratization method,and the scalar auxiliary variable method coupled with the LDG method to construct first-order temporal accurate schemes based on the gradient flow structure of the models.These semi-implicit schemes are decoupled,energy stable,and can be extended to high accuracy schemes using the semi-implicit spectral deferred correction method.Many bound preserving DG discretizations are only worked on explicit time integration methods and are difficult to get high-order accuracy.To overcome these difficulties,we use the Lagrange multipliers to enforce the implicit or semi-implicit LDG schemes to satisfy the bound constraints at each time step.This bound preserving limiter results in the Karush-Kuhn-Tucker condition,which can be solved by an efficient active set semi-smooth Newton method.Various numerical experiments illustrate the high-order accuracy and the effect of bound preserving.

关键词： Chemotaxis models Local discontinuous Galerkin(LDG)scheme Convex splitting method Variant energy quadratization method Scalar auxiliary variable method Spectral deferred correction method

Emergent symmetry in quantum phase transition:From deconfined quantum critical point to gapless quantum spin liquid

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Science Bulletin 2024年第2期69卷 190-196页

作者： Wen-Yuan Liu Shou-Shu Gong Wei-Qiang Chen zheng-Cheng gu Department of Physics The Chinese University of Hong KongHong KongChina Division of Chemistry and Chemical Engineering California Institute of TechnologyPasadena CA 91125USA School of Physical Sciences Great Bay UniversityDongguan 523000China Great Bay Institute for Advanced Study Dongguan 523000China Department of Physics and Shenzhen Institute for Quantum Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Shenzhen Key Laboratory of Advanced Quantum Functional Materials and Devices Southern University of Science and TechnologyShenzhen 518055China

The emergence of exotic quantum phenomena in frustrated magnets is rapidly driving the development of quantum many-body physics,raising fundamental questions on the nature of quantum phase transitions.Here we unveil the behaviour of emergent symmetry involving two extraordinarily representative phenomena,i.e.,the deconfined quantum critical point(DQCP)and the quantum spin liquid(QSL)state.Via large-scale tensor network simulations,we study a spatially anisotropic spin-1/2 square-lattice frustrated antiferromagnetic(AFM)model,namely the J1x-J1y-J2 model,which contains anisotropic nearestneighbor couplings J1x,J1y and the next nearest neighbor coupling J2.For small J1y/J1x,by tuning J2,a direct continuous transition between the AFM and valence bond solid phase is observed.With growing J1y/J1x,a gapless QSL phase gradually emerges between the AFM and VBS phases.We observe an emergent O(4)symmetry along the AFM–VBS transition line,which is consistent with the prediction of DQCP theory.Most surprisingly,we find that such an emergent O(4)symmetry holds for the whole QSL–VBS transition line as well.These findings reveal the intrinsic relationship between the QSL and DQCP from categorical symmetry point of view,and strongly constrain the quantum field theory description of the QSL phase.The phase diagram and critical exponents presented in this paper are of direct relevance to future experiments on frustrated magnets and cold atom systems.

关键词： Tensor network Quantum phase transition Emergent symmetry Quantum spin liquid Deconfined quantum critical point Anisotropic

Byzantine Robust Federated Learning Scheme Based on Backdoor Triggers

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Computers, Materials & Continua 2024年第5期79卷 2813-2831页

作者： zheng yang Ke gu Yiming Zuo School of Computer and Communication Engineering Changsha University of Science and TechnologyChangsha410114China

Federated learning is widely used to solve the problem of data decentralization and can provide privacy protectionfor data owners. However, since multiple participants are required in federated learning, this allows attackers tocompromise. Byzantine attacks pose great threats to federated learning. Byzantine attackers upload maliciouslycreated local models to the server to affect the prediction performance and training speed of the global model. Todefend against Byzantine attacks, we propose a Byzantine robust federated learning scheme based on backdoortriggers. In our scheme, backdoor triggers are embedded into benign data samples, and then malicious localmodels can be identified by the server according to its validation dataset. Furthermore, we calculate the adjustmentfactors of local models according to the parameters of their final layers, which are used to defend against datapoisoning-based Byzantine attacks. To further enhance the robustness of our scheme, each localmodel is weightedand aggregated according to the number of times it is identified as malicious. Relevant experimental data showthat our scheme is effective against Byzantine attacks in both independent identically distributed (IID) and nonindependentidentically distributed (non-IID) scenarios.

关键词： Federated learning Byzantine attacks backdoor triggers

Microscale spherical TiO_(2)powder prepared by hydrolysis of TiCl_(4)solution:Synthesis and kinetics

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Particuology 2024年第1期84卷 60-71页

作者： Peiyi yan Ying Zhang Shili zheng School of Rare Earths University of Science and Technology of ChinaHefei230026China Ganjiang Innovation Academy Chinese Academy of SciencesGanzhou341119China Key Laboratory of Green Process and Engineering National Engineering Research Center of Green Recycling for Strategic Metal ResourcesInstitute of Process EngineeringChinese Academy of SciencesBeijing100190China State Key Laboratory of Vanadium and Titanium Resources Comprehensive Utilization Panzhihua617000China

Hydrolysis of TiCl_(4)solution is capable of preparing microscale TiO_(2)particles.This research studied the synthesis of microscale spherical TiO_(2)powders and the hydrolysis kinetics.The effects of the flow field generated by different agitators and baffles in the crystallizer,the initial free acid concentration,the initial equivalent TiO_(2)concentration,and the temperature on the hydrolysis progress and powder morphology were systematically studied.The results show that the flow field in a crystallizer can significantly affect the morphology and particle size of the powders,and the axial flow can improve the sphericity of the powders.The increased free HCl and equivalent TiO_(2)concentrations in the pregnant solution inhibit the forward hydrolysis reaction,prolong the time to reach equilibrium,and reduce the yield.An appropriate temperature matching the compositions of the pregnant solution is crucial for the powder morphology and size.Powders with sizes ranging from around 5 um-40μm can be tuned under controlled flow field,solution compositions,and temperature conditions.In addition,the Cheng and Wunderlich modified Avrami equation was used for the crystallization kinetic modeling.The effects of the free HCl concentration,equivalent TiO_(2)concentration,and hydrolysis temperature are reflected in the reaction rate constant and active nuclei reduction index.Increasing the free HCl and equivalent TiO_(2)concentrations will reduce the reaction rate constant and accelerate the deactivation of the active nuclei,thus increasing the final powder size,while increasing the temperature will lead to the opposite results.

关键词： TiCl_(4) Hydrolysis Microscale TiO_(2) Spherical Kinetics

Mechanism Design for Ancillary Service Market Considering Social Welfare and Fairness

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 1000-1010页

作者： Zhi Wu Yuanxi Wu Wei gu zheng Xu Shu zheng Jingtao Zhao School of Electrical Engineering Southeast UniversityNanjing 210096China NARI Technology Co. Ltd.Nanjing 211106China IEEE CSEE

Increasing penetration of distributed energy resources in the distribution network(DN)is threatening safe operation of the DN,which necessitates setup of the ancillary service market in the DN.In the ancillary service market,distribution system operator(DSO)is responsible for safety of the DN by procuring available capacities of aggregators.Unlike existing studies,this paper proposes a novel market mechanism composed of two parts:choice rule and payment rule.The proposed choice rule simultaneously considers social welfare and fairness,encouraging risk-averse aggregators to participate in the ancillary service market.It is then formulated as a linear programming problem,and a distributed solution using the multi-cut Benders decomposition is presented.Moreover,successful implementation of the choice rule depends on each aggregator’s truthful adoption of private parameters.Therefore,a payment rule is also designed,which is proved to possess two properties:incentive compatibility and individual rationality.Simulation results demonstrate effectiveness of the proposed choice rule on improving fairness and verify properties of the payment rule.

关键词： Aggregator ancillary service market distributed mechanism fairness mechanism design

Small-sized Ni-Co/Mo_(2)C/Co_(6)Mo_(6)C_(2)@C for efficient alkaline and acidic hydrogen evolution reaction by an anchoring calcination strategy

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Frontiers of Chemical Science and Engineering 2024年第5期18卷 95-103页

作者： Jianxia gu Ying Zhu Haiyan zheng Chunyi Sun Zhongmin Su Department of Chemistry Xinzhou Normal UniversityXinzhou 034000China School of Chemistry Northeast Normal UniversityChangchun 130024China

A novel,cheap and highly efficient Ni-Co/Mo_(2)C/Co_(6)Mo_(6)C_(2)@C nanocomposite has been successfully constructed through simple one-step carbonization method in a nitrogen atmosphere.Polyethyleneimine in the precursor can effectively anchor molybdenum-based Keggin-type polyoxometallate and NiCo-layered double hydroxide through electrostatic and coordination interactions,which avoids the aggregation of catalyst particles during the pyrolysis process.After optimization,the obtained Ni-Co/Mo_(2)C/Co_(6)Mo_(6)C_(2)@C possesses small size(3-8 nm),large specific surface area and hierarchical pore structure.More importantly,Ni-Co/Mo_(2)C/Co_(6)Mo_(6)C_(2)@C presents remarkable hydrogen evolution reaction activity with low overpotentials in 0.5 mol·L^(-1)H_(2)SO_(4)(102.3 mV)and 1 mol·L^(-1)KOH(95 mV)to afford the current density of 10 mA·cm^(-2),as well as small Tafel slopes of 82.49 and 99.92 mV·dec^(-1),respectively.Simultaneously,this catalyst also shows outstanding stability for 12 h without a significant change in current density.The excellent catalytic performance of Ni-Co/Mo_(2)C/Co_(6)Mo_(6)C_(2)@C can put down to the synergistic effect between multiple components and the small size of the catalyst.This work provides unique insights into the preparation of efficient transition metal-based catalysts for HER.

关键词： polyoxometallates layered double hydroxide transition metal-based electrocatalysts hydrogen evolution reaction