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EGFR-targeted and gemcitabine-incorporated chemogene for combinatorial pancreatic cancer treatment

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Nano Research 2024年第2期17卷 848-857页

作者： Miao Xie Qiushuang Zhang Yuanyuan Guo Lijuan zhu Xinyuan zhu chuan Zhang School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesInstitute of Molecular MedicineSixth people’s HospitalSchool of MedicineShanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong UniversityShanghai 200240China Department of Radiology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200233China Institute of Molecular Medicine Shanghai Jiao Tong University Affiliated Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Pancreatic cancer stands out as a recognized intractable tumor due to its high malignancy and mortality rates,which are largely attributed to the insensitivity of current clinical chemotherapies or multidrug-resistance.Combinatorial chemo and gene therapy that integrates different therapeutic targets,may increase the chemosensitivity of pancreatic cancer and synergistically enhance the antitumor efficacy.However,conventional co-delivery of gene and chemo drugs is intensively dependent on complex nanoparticle delivery systems,thus would be limited by unstable drug packaging,nonspecific biodistribution,and biosafety problem.Herein,we rationally designed an epidermal growth factor-receptor(EGFR)-targeted and gemcitabine-incorporated oligonucleotide(termed as chemogene)with anti-Bcl-2 sequence,which achieves simple and precise integration of gemcitabine into a gene regulative agent,as well as the EGFR-targeted delivery for pancreatic cancer therapy.Through solid-phase synthesis,gemcitabine,as the first-line chemodrug for pancreatic cancer,is introduced to the antisense oligonucleotide to replace all cytosine nucleosides to obtain the gemcitabine-integrated chemogene(Ge-ASO^(Bcl-2)).Thereafter,Ge-ASO^(Bcl-2)is covalently coupled with EGFR nanobody to construct the final targeted chemogene without any exogenous carriers.Notably,this nanobody-conjugated chemogene exhibits remarkable tumor targeting capability and antitumor effects both in vitro and in vivo,which initiates a first step toward the application of combinatorial chemo and gene therapy for future pancreatic cancer treatment.

关键词： antisense oligonucleotide chemogene nanobody drug delivery system pancreatic cancer

Carbon-based interface engineering and architecture design for high-performance lithium metal anodes

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Carbon Energy 2024年第1期6卷 207-235页

作者： Na zhu Yuxiang Yang Yu Li Ying Bai Junfeng Rong chuan Wu SINOPEC Research Institute of Petroleum Processing Co. Ltd.BeijingChina Beijing Key Laboratory of Environmental Science and Engineering School of Materials Science and EngineeringBeijing Institute of TechnologyBeijingChina Yangtze Delta Region Academy of Beijing Institute of Technology JiaxingChina

Metallic lithium(Li)is considered the“Holy Grail”anode material for the nextgeneration of Li batteries with high energy density owing to the extraordinary theoretical specific capacity and the lowest negative electrochemical potential.However,owing to inhomogeneous Li-ion flux,Li anodes undergo uncontrollable Li deposition,leading to limited power output and practical applications.Carbon materials and their composites with controllable structures and properties have received extensive attention to guide the homogeneous growth of Li to achieve high-performance Li anodes.In this review,the correlation between the behavior of Li anode and the properties of carbon materials is proposed.Subsequently,we review emerging strategies for rationally designing high-performance Li anodes with carbon materials,including interface engineering(stabilizing solid electrolyte interphase layer and other functionalized interfacial layer)and architecture design of host carbon(constructing three-dimension structure,preparing hollow structure,introducing lithiophilic sites,optimizing geometric effects,and compositing with Li).Based on the insights,some prospects on critical challenges and possible future research directions in this field are concluded.It is anticipated that further innovative works on the fundamental chemistry and theoretical research of Li anodes are needed.

关键词： carbon materials dendrites hosts interfacial layers Li metal anodes

Advances in the differentiation of pluripotent stem cells into vascular cells

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World Journal of Stem Cells 2024年第2期16卷 137-150页

作者： Yi-Chang Jiao Ying-Xin Wang Wen-zhu Liu Jing-Wen Xu Yu-Ying Zhao chuan-zhu Yan Fu-Chen Liu Department of Neurology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Mitochondrial Medicine Laboratory Qilu Hospital(Qingdao)of Shandong UniversityQingdao 266103Shandong ProvinceChina Brain Science Research Institute Shandong UniversityJinan 250012Shandong ProvinceChina

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

关键词： Induced pluripotent stem cell Blood vessels Vascular organoids Endothelial cells Smooth muscle cells Pericytes Tissue engineering vascular graft

Gradient sparsification for efficient wireless federated learning with differential privacy

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Science China(Information Sciences) 2024年第4期67卷 272-288页

作者： Kang WEI Jun LI chuan MA Ming DING Feng SHU Haitao ZHAO Wen CHEN Hongbo zhu School of Electronic and Optical Engineering Nanjing University of Science and Technology Zhejiang Lab Key Laboratory of Computer Network and Information Integration(Southeast University) Ministry of Education Data61 Commonwealth Scientific and Industrial Research Organisation School of Information and Communication Engineering Hainan University School of Communications and Information Engineering Nanjing University of Posts and Telecommunications School of Electronic Information and Electrical Engineering Shanghai Jiao Tong University

Federated learning(FL) enables distributed clients to collaboratively train a machine learning model without sharing raw data with each other. However, it suffers from the leakage of private information from uploading models. In addition, as the model size grows, the training latency increases due to the limited transmission bandwidth and model performance degradation while using differential privacy(DP)protection. In this paper, we propose a gradient sparsification empowered FL framework with DP over wireless channels, to improve training efficiency without sacrificing convergence performance. Specifically, we first design a random sparsification algorithm to retain a fraction of the gradient elements in each client’s local model, thereby mitigating the performance degradation induced by DP and reducing the number of transmission parameters over wireless channels. Then, we analyze the convergence bound of the proposed algorithm, by modeling a non-convex FL problem. Next, we formulate a time-sequential stochastic optimization problem for minimizing the developed convergence bound, under the constraints of transmit power, the average transmitting delay, as well as the client’s DP requirement. Utilizing the Lyapunov drift-plus-penalty framework, we develop an analytical solution to the optimization problem. Extensive experiments have been implemented on three real-life datasets to demonstrate the effectiveness of our proposed algorithm. We show that our proposed algorithms can fully exploit the interworking between communication and computation to outperform the baselines, i.e., random scheduling, round robin, and delay-minimization algorithms.

关键词： federated learning differential privacy gradient sparsification Lyapunov drift convergence analysis

Expedient Trifluoromethylacylation of Styrenes Enabled by Photoredox Catalysis

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Chinese Journal of Chemistry 2022年第1期40卷 59-64页

作者： Lu Wang Heng Zhang chuan zhu Chao Feng Technical Institute of Fluorochemistry(TIF) Institute of Advanced Synthesis(IAS)School of Chemistry and Molecular EngineeringNanjing Tech University30 South Puzhu RoadNanjingJiangsu 211816China

Herein,we disclosed a photoredox enabled protocol for trifluoromethylacylation of styrenes through a radical-carboanion cascade and subsequent oxidation.With a broad range of aldehydes and inexpensive Langlois reagent as acyl and CF3 precursor,respectively,the alkene motif could be readily converted into β-trifluoromethyl ketones in moderate to good yields and with excellent regioselectivity.Besides CF3,di-,mono-and non-fluorinated C-radicals were revealed amenable in this reaction,providing good opportunity for the construction of structurally diverse ketones of interest in pharmaceutical research.Additionally,the utility of this protocol was further demonstrated by successful extension to trifluoromethylarylation and-alkylation by employing arylcyanide or acrylates in place of carbonyls.

关键词： Trifluoromethylacylation Alkenes Photocatalysis CF_(3)radical Radical-polar crossover

Microstructure Recrystallization and Mechanical Properties of a Cold-Rolled TiNbZrTaHf Refractory High-Entropy Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第4期37卷 633-647页

作者： chuan Rong Jieren Yang Xiaoliang Zhao Ke Huang Ying Liu Xiaohong Wang Dongdong zhu Ruirun Chen College of Materials Science and Engineering Sichuan UniversityChengdu610065China Key Laboratory of Air-Driven Equipment Technology of Zhejiang Province Quzhou UniversityQuzhou324000China School of Materials Science and Engineering Harbin Institute of TechnologyHarbin150001China

The equiatomic TiNbZrTaHf alloy was successfully rolled at room temperature with the reduction of ~ 85%. The microstructure and tensile properties were investigated after cold working and annealing. It was determined that the recrystallization temperature of the TiNbZrTaHf alloy between 850 and 900 ℃. Complete recrystallization and normal grain growth occurred, the high stability of single phase was maintained after annealing at 1000, 1200, and 1400 ℃. But the precipitated phase appeared after long term annealing, as seen after 500 h at 1000 ℃. After cold working, the tensile strength and the elongation of TiNbZrTaHf were 1137 MPa and 25.1%, respectively. The annealed alloy has a high tensile strength (σ_(b )= 863 MPa) and ductility (ε_(e )= 28.5%). Moreover, the oxidation of TiNbZrTaHf alloy at elevated temperatures has a significant impact on its mechanical properties. The poor oxidation resistance of TiNbZrTaHf can accelerate tensile failure by inducing fractures at grain boundaries.

关键词： Refractory high entropy alloy Cold rolling Recrystallization Oxidation resistance Mechanical properties

Animal models of hepatitis E infection: Advances and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 171-180页

作者： Ze Xiang Xiang-Lin He chuan-Wu zhu Jia-Jia Yang Lan Huang Chun Jiang Jian Wu Chinese Consortium for the Study of Hepatitis E(CCSHE) Zhejiang University School of Medicine Hangzhou 310030China Department of Infectious Diseases The Fifth People’s Hospital of SuzhouSuzhou 215007China Department of Infection Management The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China Department of Clinical Laboratory The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China 不详

Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and jaundice.HEV infection may become chronic in immunosuppressed individuals.In addition,HEV infection can also cause several extrahepatic manifestations.HEV exists in a wide range of hosts in nature and can be transmitted across species.Hence,animals susceptible to HEV can be used as models.The establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis E.This review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other animals.For each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV infection.The advantages and disadvantages of these animal models were also emphasized.This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

关键词： Hepatitis E virus Animal models Pathogenesis Prevention Treatment

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Remote entangling gate between a quantum dot spin and a transmon qubit mediated by microwave photons

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Chinese Physics B 2024年第2期33卷 52-59页

作者：朱行宇朱乐天涂涛李传锋 Key Laboratory of Quantum Information Chinese Academy of SciencesUniversity of Science and Technology of ChinaHefei 230026China School of Mechanical and Electronic Engineering Suzhou UniversitySuzhou 234000China Hefei National Laboratory University of Science and Technology of ChinaChinese Academy of SciencesHefei 230088China

Spin qubits and superconducting qubits are promising candidates for realizing solid-state quantum information processors.Designing a hybrid architecture that combines the advantages of different qubits on the same chip is a highly desirable but challenging goal.Here we propose a hybrid architecture that utilizes a high-impedance SQUID array resonator as a quantum bus,thereby coherently coupling different solid-state qubits.We employ a resonant exchange spin qubit hosted in a triple quantum dot and a superconducting transmon qubit.Since this hybrid system is highly tunable,it can operate in a dispersive regime,where the interaction between the different qubits is mediated by virtual photons.By utilizing such interactions,entangling gate operations between different qubits can be realized in a short time of 30 ns with a fidelity of up to 96.5%under realistic parameter conditions.Further utilizing this interaction,remote entangled state between different qubits can be prepared and is robust to perturbations of various parameters.These results pave the way for exploring efficient fault-tolerant quantum computation on hybrid quantum architecture platforms.

关键词： hybrid quantum architectures circuit quantum electrodynamics entangling gate

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Constructing highly safe and long-life calcium ion batteries based on hydratedvanadium oxide cathodes featuring a pillar structure

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Rare Metals 2024年第6期43卷 2597-2612页

作者： Chun-Fang Wang Shi-Wei Zhang Lan Huang Yuan-Min zhu Feng Liu Jian-chuan Wang Li-Ming Tan Chun-Yi Zhi Cui-Ping Han Powder Metallurgy Research Institute Central South University Songshan Lake Materials Laboratory Research Institute of Interdisciplinary Science and School of Materials Science and Engineering Dongguan University of Technology Department of Materials Science and Engineering City University of Hong Kong Faculty of Materials Science and Energy Engineering/Institute of Technology for Carbon Neutrality Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences

Calcium-ion batteries（CIBs） have generated intense interest due to the growing demand for safer,cheaper,and large-scale energy storage systems.However,their development is still in its infancy,owing to the lack of suitable cathodes for sustaining reversiblc Ca2+intercalation/deintercalation.Herein,layered H2V3O8（HVO） with Zn2+pre-insertion（ZHVO） is reported as a high-rate and highly durable cathode material for CIBs.The existence of Zn2+and H2O pillars could expand the interlayer spacing up to 1.8 nm,which is favorable for the diffusion of bulky Ca2+.The formation of Zn-O bonds facilitates electron transfer and enhances electrical conduction.Consequently,the ZHVO cathode achieves superior capacity performance(213.9 mAh·g-1at 0.2 A·g-1) and long lifespan(78.3% for 1,000 cycles at 5 A·g-1) compared to pristine HVO.Density functional theory（DFT） calculations revealed that Zn2+moved during Ca2+intercalation,thereby reducing the diffusion energy barrier and facilitating Ca2+diffusion.Finally,a safe aqueous calcium ion cell was successfully assembled.

关键词： Multivalent batteries Calcium-ion batteries Layered structure Vanadium oxide Cathode materials